ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5266dup (p.Gln1756fs)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Apr 2016 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.5266dup (p.Gln1756fs)
Variation ID: 17677 Accession: VCV000017677.134
- Type and length
-
Duplication, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43057062-43057063 (GRCh38) [ NCBI UCSC ] 17: 41209079-41209080 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 1, 2013 Nov 24, 2024 Apr 22, 2016 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5266dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Gln1756fs frameshift NM_007294.4:c.5266dupC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
frameshift NM_001407571.1:c.5051dup NP_001394500.1:p.Gln1685Profs frameshift NM_001407581.1:c.5330dup NP_001394510.1:p.Gln1778Profs frameshift NM_001407582.1:c.5330dup NP_001394511.1:p.Gln1778Profs frameshift NM_001407583.1:c.5327dup NP_001394512.1:p.Gln1777Profs frameshift NM_001407585.1:c.5327dup NP_001394514.1:p.Gln1777Profs frameshift NM_001407587.1:c.5327dup NP_001394516.1:p.Gln1777Profs frameshift NM_001407590.1:c.5324dup NP_001394519.1:p.Gln1776Profs frameshift NM_001407591.1:c.5324dup NP_001394520.1:p.Gln1776Profs frameshift NM_001407593.1:c.5264dup NP_001394522.1:p.Gln1756Profs frameshift NM_001407594.1:c.5264dup NP_001394523.1:p.Gln1756Profs frameshift NM_001407596.1:c.5264dup NP_001394525.1:p.Gln1756Profs frameshift NM_001407597.1:c.5264dup NP_001394526.1:p.Gln1756Profs frameshift NM_001407598.1:c.5264dup NP_001394527.1:p.Gln1756Profs frameshift NM_001407602.1:c.5264dup NP_001394531.1:p.Gln1756Profs frameshift NM_001407603.1:c.5264dup NP_001394532.1:p.Gln1756Profs frameshift NM_001407605.1:c.5264dup NP_001394534.1:p.Gln1756Profs frameshift NM_001407610.1:c.5261dup NP_001394539.1:p.Gln1755Profs frameshift NM_001407611.1:c.5261dup NP_001394540.1:p.Gln1755Profs frameshift NM_001407612.1:c.5261dup NP_001394541.1:p.Gln1755Profs frameshift NM_001407613.1:c.5261dup NP_001394542.1:p.Gln1755Profs frameshift NM_001407614.1:c.5261dup NP_001394543.1:p.Gln1755Profs frameshift NM_001407615.1:c.5261dup NP_001394544.1:p.Gln1755Profs frameshift NM_001407616.1:c.5261dup NP_001394545.1:p.Gln1755Profs frameshift NM_001407617.1:c.5261dup NP_001394546.1:p.Gln1755Profs frameshift NM_001407618.1:c.5261dup NP_001394547.1:p.Gln1755Profs frameshift NM_001407619.1:c.5261dup NP_001394548.1:p.Gln1755Profs frameshift NM_001407620.1:c.5261dup NP_001394549.1:p.Gln1755Profs frameshift NM_001407621.1:c.5261dup NP_001394550.1:p.Gln1755Profs frameshift NM_001407622.1:c.5261dup NP_001394551.1:p.Gln1755Profs frameshift NM_001407623.1:c.5261dup NP_001394552.1:p.Gln1755Profs frameshift NM_001407624.1:c.5261dup NP_001394553.1:p.Gln1755Profs frameshift NM_001407625.1:c.5261dup NP_001394554.1:p.Gln1755Profs frameshift NM_001407626.1:c.5261dup NP_001394555.1:p.Gln1755Profs frameshift NM_001407627.1:c.5258dup NP_001394556.1:p.Gln1754Profs frameshift NM_001407628.1:c.5258dup NP_001394557.1:p.Gln1754Profs frameshift NM_001407629.1:c.5258dup NP_001394558.1:p.Gln1754Profs frameshift NM_001407630.1:c.5258dup NP_001394559.1:p.Gln1754Profs frameshift NM_001407631.1:c.5258dup NP_001394560.1:p.Gln1754Profs frameshift NM_001407632.1:c.5258dup NP_001394561.1:p.Gln1754Profs frameshift NM_001407633.1:c.5258dup NP_001394562.1:p.Gln1754Profs frameshift NM_001407634.1:c.5258dup NP_001394563.1:p.Gln1754Profs frameshift NM_001407635.1:c.5258dup NP_001394564.1:p.Gln1754Profs frameshift NM_001407636.1:c.5258dup NP_001394565.1:p.Gln1754Profs frameshift NM_001407637.1:c.5258dup NP_001394566.1:p.Gln1754Profs frameshift NM_001407638.1:c.5258dup NP_001394567.1:p.Gln1754Profs frameshift NM_001407639.1:c.5258dup NP_001394568.1:p.Gln1754Profs frameshift NM_001407640.1:c.5258dup NP_001394569.1:p.Gln1754Profs frameshift NM_001407641.1:c.5258dup NP_001394570.1:p.Gln1754Profs frameshift NM_001407642.1:c.5258dup NP_001394571.1:p.Gln1754Profs frameshift NM_001407644.1:c.5255dup NP_001394573.1:p.Gln1753Profs frameshift NM_001407645.1:c.5255dup NP_001394574.1:p.Gln1753Profs frameshift NM_001407646.1:c.5252dup NP_001394575.1:p.Gln1752Profs frameshift NM_001407647.1:c.5249dup NP_001394576.1:p.Gln1751Profs frameshift NM_001407648.1:c.5207dup NP_001394577.1:p.Gln1737Profs frameshift NM_001407649.1:c.5204dup NP_001394578.1:p.Gln1736Profs frameshift NM_001407652.1:c.5186dup NP_001394581.1:p.Gln1730Profs frameshift NM_001407653.1:c.5186dup NP_001394582.1:p.Gln1730Profs frameshift NM_001407654.1:c.5186dup NP_001394583.1:p.Gln1730Profs frameshift NM_001407655.1:c.5186dup NP_001394584.1:p.Gln1730Profs frameshift NM_001407656.1:c.5183dup NP_001394585.1:p.Gln1729Profs frameshift NM_001407657.1:c.5183dup NP_001394586.1:p.Gln1729Profs frameshift NM_001407658.1:c.5183dup NP_001394587.1:p.Gln1729Profs frameshift NM_001407659.1:c.5180dup NP_001394588.1:p.Gln1728Profs frameshift NM_001407660.1:c.5180dup NP_001394589.1:p.Gln1728Profs frameshift NM_001407661.1:c.5180dup NP_001394590.1:p.Gln1728Profs frameshift NM_001407662.1:c.5180dup NP_001394591.1:p.Gln1728Profs frameshift NM_001407663.1:c.5180dup NP_001394592.1:p.Gln1728Profs frameshift NM_001407664.1:c.5141dup NP_001394593.1:p.Gln1715Profs frameshift NM_001407665.1:c.5141dup NP_001394594.1:p.Gln1715Profs frameshift NM_001407666.1:c.5141dup NP_001394595.1:p.Gln1715Profs frameshift NM_001407667.1:c.5141dup NP_001394596.1:p.Gln1715Profs frameshift NM_001407668.1:c.5141dup NP_001394597.1:p.Gln1715Profs frameshift NM_001407669.1:c.5141dup NP_001394598.1:p.Gln1715Profs frameshift NM_001407670.1:c.5138dup NP_001394599.1:p.Gln1714Profs frameshift NM_001407671.1:c.5138dup NP_001394600.1:p.Gln1714Profs frameshift NM_001407672.1:c.5138dup NP_001394601.1:p.Gln1714Profs frameshift NM_001407673.1:c.5138dup NP_001394602.1:p.Gln1714Profs frameshift NM_001407674.1:c.5138dup NP_001394603.1:p.Gln1714Profs frameshift NM_001407675.1:c.5138dup NP_001394604.1:p.Gln1714Profs frameshift NM_001407676.1:c.5138dup NP_001394605.1:p.Gln1714Profs frameshift NM_001407677.1:c.5138dup NP_001394606.1:p.Gln1714Profs frameshift NM_001407678.1:c.5138dup NP_001394607.1:p.Gln1714Profs frameshift NM_001407679.1:c.5138dup NP_001394608.1:p.Gln1714Profs frameshift NM_001407680.1:c.5138dup NP_001394609.1:p.Gln1714Profs frameshift NM_001407681.1:c.5135dup NP_001394610.1:p.Gln1713Profs frameshift NM_001407682.1:c.5135dup NP_001394611.1:p.Gln1713Profs frameshift NM_001407683.1:c.5135dup NP_001394612.1:p.Gln1713Profs frameshift NM_001407684.1:c.5264dup NP_001394613.1:p.Gln1756Profs frameshift NM_001407685.1:c.5135dup NP_001394614.1:p.Gln1713Profs frameshift NM_001407686.1:c.5135dup NP_001394615.1:p.Gln1713Profs frameshift NM_001407687.1:c.5135dup NP_001394616.1:p.Gln1713Profs frameshift NM_001407688.1:c.5135dup NP_001394617.1:p.Gln1713Profs frameshift NM_001407689.1:c.5135dup NP_001394618.1:p.Gln1713Profs frameshift NM_001407690.1:c.5132dup NP_001394619.1:p.Gln1712Profs frameshift NM_001407691.1:c.5132dup NP_001394620.1:p.Gln1712Profs frameshift NM_001407692.1:c.5123dup NP_001394621.1:p.Gln1709Profs frameshift NM_001407694.1:c.5123dup NP_001394623.1:p.Gln1709Profs frameshift NM_001407695.1:c.5123dup NP_001394624.1:p.Gln1709Profs frameshift NM_001407696.1:c.5123dup NP_001394625.1:p.Gln1709Profs frameshift NM_001407697.1:c.5123dup NP_001394626.1:p.Gln1709Profs frameshift NM_001407698.1:c.5123dup NP_001394627.1:p.Gln1709Profs frameshift NM_001407724.1:c.5123dup NP_001394653.1:p.Gln1709Profs frameshift NM_001407725.1:c.5123dup NP_001394654.1:p.Gln1709Profs frameshift NM_001407726.1:c.5123dup NP_001394655.1:p.Gln1709Profs frameshift NM_001407727.1:c.5123dup NP_001394656.1:p.Gln1709Profs frameshift NM_001407728.1:c.5123dup NP_001394657.1:p.Gln1709Profs frameshift NM_001407729.1:c.5123dup NP_001394658.1:p.Gln1709Profs frameshift NM_001407730.1:c.5123dup NP_001394659.1:p.Gln1709Profs frameshift NM_001407731.1:c.5123dup NP_001394660.1:p.Gln1709Profs frameshift NM_001407732.1:c.5120dup NP_001394661.1:p.Gln1708Profs frameshift NM_001407733.1:c.5120dup NP_001394662.1:p.Gln1708Profs frameshift NM_001407734.1:c.5120dup NP_001394663.1:p.Gln1708Profs frameshift NM_001407735.1:c.5120dup NP_001394664.1:p.Gln1708Profs frameshift NM_001407736.1:c.5120dup NP_001394665.1:p.Gln1708Profs frameshift NM_001407737.1:c.5120dup NP_001394666.1:p.Gln1708Profs frameshift NM_001407738.1:c.5120dup NP_001394667.1:p.Gln1708Profs frameshift NM_001407739.1:c.5120dup NP_001394668.1:p.Gln1708Profs frameshift NM_001407740.1:c.5120dup NP_001394669.1:p.Gln1708Profs frameshift NM_001407741.1:c.5120dup NP_001394670.1:p.Gln1708Profs frameshift NM_001407742.1:c.5120dup NP_001394671.1:p.Gln1708Profs frameshift NM_001407743.1:c.5120dup NP_001394672.1:p.Gln1708Profs frameshift NM_001407744.1:c.5120dup NP_001394673.1:p.Gln1708Profs frameshift NM_001407745.1:c.5120dup NP_001394674.1:p.Gln1708Profs frameshift NM_001407746.1:c.5120dup NP_001394675.1:p.Gln1708Profs frameshift NM_001407747.1:c.5120dup NP_001394676.1:p.Gln1708Profs frameshift NM_001407748.1:c.5120dup NP_001394677.1:p.Gln1708Profs frameshift NM_001407749.1:c.5120dup NP_001394678.1:p.Gln1708Profs frameshift NM_001407750.1:c.5120dup NP_001394679.1:p.Gln1708Profs frameshift NM_001407751.1:c.5120dup NP_001394680.1:p.Gln1708Profs frameshift NM_001407752.1:c.5120dup NP_001394681.1:p.Gln1708Profs frameshift NM_001407838.1:c.5117dup NP_001394767.1:p.Gln1707Profs frameshift NM_001407839.1:c.5117dup NP_001394768.1:p.Gln1707Profs frameshift NM_001407841.1:c.5117dup NP_001394770.1:p.Gln1707Profs frameshift NM_001407842.1:c.5117dup NP_001394771.1:p.Gln1707Profs frameshift NM_001407843.1:c.5117dup NP_001394772.1:p.Gln1707Profs frameshift NM_001407844.1:c.5117dup NP_001394773.1:p.Gln1707Profs frameshift NM_001407845.1:c.5117dup NP_001394774.1:p.Gln1707Profs frameshift NM_001407846.1:c.5117dup NP_001394775.1:p.Gln1707Profs frameshift NM_001407847.1:c.5117dup NP_001394776.1:p.Gln1707Profs frameshift NM_001407848.1:c.5117dup NP_001394777.1:p.Gln1707Profs frameshift NM_001407849.1:c.5117dup NP_001394778.1:p.Gln1707Profs frameshift NM_001407850.1:c.5117dup NP_001394779.1:p.Gln1707Profs frameshift NM_001407851.1:c.5117dup NP_001394780.1:p.Gln1707Profs frameshift NM_001407852.1:c.5117dup NP_001394781.1:p.Gln1707Profs frameshift NM_001407853.1:c.5117dup NP_001394782.1:p.Gln1707Profs frameshift NM_001407854.1:c.5264dup NP_001394783.1:p.Gln1756Profs frameshift NM_001407858.1:c.5261dup NP_001394787.1:p.Gln1755Profs frameshift NM_001407859.1:c.5261dup NP_001394788.1:p.Gln1755Profs frameshift NM_001407860.1:c.5261dup NP_001394789.1:p.Gln1755Profs frameshift NM_001407861.1:c.5258dup NP_001394790.1:p.Gln1754Profs frameshift NM_001407862.1:c.5063dup NP_001394791.1:p.Gln1689Profs frameshift NM_001407863.1:c.5060dup NP_001394792.1:p.Gln1688Profs frameshift NM_001407874.1:c.5057dup NP_001394803.1:p.Gln1687Profs frameshift NM_001407875.1:c.5057dup NP_001394804.1:p.Gln1687Profs frameshift NM_001407879.1:c.5054dup NP_001394808.1:p.Gln1686Profs frameshift NM_001407881.1:c.5054dup NP_001394810.1:p.Gln1686Profs frameshift NM_001407882.1:c.5054dup NP_001394811.1:p.Gln1686Profs frameshift NM_001407884.1:c.5054dup NP_001394813.1:p.Gln1686Profs frameshift NM_001407885.1:c.5054dup NP_001394814.1:p.Gln1686Profs frameshift NM_001407886.1:c.5054dup NP_001394815.1:p.Gln1686Profs frameshift NM_001407887.1:c.5054dup NP_001394816.1:p.Gln1686Profs frameshift NM_001407889.1:c.5054dup NP_001394818.1:p.Gln1686Profs frameshift NM_001407894.1:c.5051dup NP_001394823.1:p.Gln1685Profs frameshift NM_001407895.1:c.5051dup NP_001394824.1:p.Gln1685Profs frameshift NM_001407896.1:c.5051dup NP_001394825.1:p.Gln1685Profs frameshift NM_001407897.1:c.5051dup NP_001394826.1:p.Gln1685Profs frameshift NM_001407898.1:c.5051dup NP_001394827.1:p.Gln1685Profs frameshift NM_001407899.1:c.5051dup NP_001394828.1:p.Gln1685Profs frameshift NM_001407900.1:c.5051dup NP_001394829.1:p.Gln1685Profs frameshift NM_001407902.1:c.5051dup NP_001394831.1:p.Gln1685Profs frameshift NM_001407904.1:c.5051dup NP_001394833.1:p.Gln1685Profs frameshift NM_001407906.1:c.5051dup NP_001394835.1:p.Gln1685Profs frameshift NM_001407907.1:c.5051dup NP_001394836.1:p.Gln1685Profs frameshift NM_001407908.1:c.5051dup NP_001394837.1:p.Gln1685Profs frameshift NM_001407909.1:c.5051dup NP_001394838.1:p.Gln1685Profs frameshift NM_001407910.1:c.5051dup NP_001394839.1:p.Gln1685Profs frameshift NM_001407915.1:c.5048dup NP_001394844.1:p.Gln1684Profs frameshift NM_001407916.1:c.5048dup NP_001394845.1:p.Gln1684Profs frameshift NM_001407917.1:c.5048dup NP_001394846.1:p.Gln1684Profs frameshift NM_001407918.1:c.5048dup NP_001394847.1:p.Gln1684Profs frameshift NM_001407919.1:c.5141dup NP_001394848.1:p.Gln1715Profs frameshift NM_001407920.1:c.5000dup NP_001394849.1:p.Gln1668Profs frameshift NM_001407921.1:c.5000dup NP_001394850.1:p.Gln1668Profs frameshift NM_001407922.1:c.5000dup NP_001394851.1:p.Gln1668Profs frameshift NM_001407923.1:c.5000dup NP_001394852.1:p.Gln1668Profs frameshift NM_001407924.1:c.5000dup NP_001394853.1:p.Gln1668Profs frameshift NM_001407925.1:c.5000dup NP_001394854.1:p.Gln1668Profs frameshift NM_001407926.1:c.5000dup NP_001394855.1:p.Gln1668Profs frameshift NM_001407927.1:c.4997dup NP_001394856.1:p.Gln1667Profs frameshift NM_001407928.1:c.4997dup NP_001394857.1:p.Gln1667Profs frameshift NM_001407929.1:c.4997dup NP_001394858.1:p.Gln1667Profs frameshift NM_001407930.1:c.4997dup NP_001394859.1:p.Gln1667Profs frameshift NM_001407931.1:c.4997dup NP_001394860.1:p.Gln1667Profs frameshift NM_001407932.1:c.4997dup NP_001394861.1:p.Gln1667Profs frameshift NM_001407933.1:c.4997dup NP_001394862.1:p.Gln1667Profs frameshift NM_001407934.1:c.4994dup NP_001394863.1:p.Gln1666Profs frameshift NM_001407935.1:c.4994dup NP_001394864.1:p.Gln1666Profs frameshift NM_001407936.1:c.4994dup NP_001394865.1:p.Gln1666Profs frameshift NM_001407937.1:c.5141dup NP_001394866.1:p.Gln1715Profs frameshift NM_001407938.1:c.5141dup NP_001394867.1:p.Gln1715Profs frameshift NM_001407939.1:c.5138dup NP_001394868.1:p.Gln1714Profs frameshift NM_001407940.1:c.5138dup NP_001394869.1:p.Gln1714Profs frameshift NM_001407941.1:c.5135dup NP_001394870.1:p.Gln1713Profs frameshift NM_001407942.1:c.5123dup NP_001394871.1:p.Gln1709Profs frameshift NM_001407943.1:c.5120dup NP_001394872.1:p.Gln1708Profs frameshift NM_001407944.1:c.5120dup NP_001394873.1:p.Gln1708Profs frameshift NM_001407945.1:c.5120dup NP_001394874.1:p.Gln1708Profs frameshift NM_001407946.1:c.4931dup NP_001394875.1:p.Gln1645Profs frameshift NM_001407947.1:c.4931dup NP_001394876.1:p.Gln1645Profs frameshift NM_001407948.1:c.4931dup NP_001394877.1:p.Gln1645Profs frameshift NM_001407949.1:c.4931dup NP_001394878.1:p.Gln1645Profs frameshift NM_001407950.1:c.4928dup NP_001394879.1:p.Gln1644Profs frameshift NM_001407951.1:c.4928dup NP_001394880.1:p.Gln1644Profs frameshift NM_001407952.1:c.4928dup NP_001394881.1:p.Gln1644Profs frameshift NM_001407953.1:c.4928dup NP_001394882.1:p.Gln1644Profs frameshift NM_001407954.1:c.4928dup NP_001394883.1:p.Gln1644Profs frameshift NM_001407955.1:c.4928dup NP_001394884.1:p.Gln1644Profs frameshift NM_001407956.1:c.4925dup NP_001394885.1:p.Gln1643Profs frameshift NM_001407957.1:c.4925dup NP_001394886.1:p.Gln1643Profs frameshift NM_001407958.1:c.4925dup NP_001394887.1:p.Gln1643Profs frameshift NM_001407959.1:c.4883dup NP_001394888.1:p.Gln1629Profs frameshift NM_001407960.1:c.4880dup NP_001394889.1:p.Gln1628Profs frameshift NM_001407962.1:c.4880dup NP_001394891.1:p.Gln1628Profs frameshift NM_001407963.1:c.4877dup NP_001394892.1:p.Gln1627Profs frameshift NM_001407964.1:c.4802dup NP_001394893.1:p.Gln1602Profs frameshift NM_001407965.1:c.4757dup NP_001394894.1:p.Gln1587Profs frameshift NM_001407966.1:c.4376dup NP_001394895.1:p.Gln1460Profs frameshift NM_001407967.1:c.4373dup NP_001394896.1:p.Gln1459Profs frameshift NM_001407968.1:c.2660dup NP_001394897.1:p.Gln888Profs frameshift NM_001407969.1:c.2657dup NP_001394898.1:p.Gln887Profs frameshift NM_001407970.1:c.2021dup NP_001394899.1:p.Gln675Profs frameshift NM_001407971.1:c.2021dup NP_001394900.1:p.Gln675Profs frameshift NM_001407972.1:c.2018dup NP_001394901.1:p.Gln674Profs frameshift NM_001407973.1:c.1955dup NP_001394902.1:p.Gln653Profs frameshift NM_001407974.1:c.1955dup NP_001394903.1:p.Gln653Profs frameshift NM_001407975.1:c.1955dup NP_001394904.1:p.Gln653Profs frameshift NM_001407976.1:c.1955dup NP_001394905.1:p.Gln653Profs frameshift NM_001407977.1:c.1955dup NP_001394906.1:p.Gln653Profs frameshift NM_001407978.1:c.1955dup NP_001394907.1:p.Gln653Profs frameshift NM_001407979.1:c.1952dup NP_001394908.1:p.Gln652Profs frameshift NM_001407980.1:c.1952dup NP_001394909.1:p.Gln652Profs frameshift NM_001407981.1:c.1952dup NP_001394910.1:p.Gln652Profs frameshift NM_001407982.1:c.1952dup NP_001394911.1:p.Gln652Profs frameshift NM_001407983.1:c.1952dup NP_001394912.1:p.Gln652Profs frameshift NM_001407984.1:c.1952dup NP_001394913.1:p.Gln652Profs frameshift NM_001407985.1:c.1952dup NP_001394914.1:p.Gln652Profs frameshift NM_001407986.1:c.1952dup NP_001394915.1:p.Gln652Profs frameshift NM_001407990.1:c.1952dup NP_001394919.1:p.Gln652Profs frameshift NM_001407991.1:c.1952dup NP_001394920.1:p.Gln652Profs frameshift NM_001407992.1:c.1952dup NP_001394921.1:p.Gln652Profs frameshift NM_001407993.1:c.1952dup NP_001394922.1:p.Gln652Profs frameshift NM_001408392.1:c.1949dup NP_001395321.1:p.Gln651Profs frameshift NM_001408396.1:c.1949dup NP_001395325.1:p.Gln651Profs frameshift NM_001408397.1:c.1949dup NP_001395326.1:p.Gln651Profs frameshift NM_001408398.1:c.1949dup NP_001395327.1:p.Gln651Profs frameshift NM_001408399.1:c.1949dup NP_001395328.1:p.Gln651Profs frameshift NM_001408400.1:c.1949dup NP_001395329.1:p.Gln651Profs frameshift NM_001408401.1:c.1949dup NP_001395330.1:p.Gln651Profs frameshift NM_001408402.1:c.1949dup NP_001395331.1:p.Gln651Profs frameshift NM_001408403.1:c.1949dup NP_001395332.1:p.Gln651Profs frameshift NM_001408404.1:c.1949dup NP_001395333.1:p.Gln651Profs frameshift NM_001408406.1:c.1946dup NP_001395335.1:p.Gln650Profs frameshift NM_001408407.1:c.1946dup NP_001395336.1:p.Gln650Profs frameshift NM_001408408.1:c.1946dup NP_001395337.1:p.Gln650Profs frameshift NM_001408409.1:c.1943dup NP_001395338.1:p.Gln649Profs frameshift NM_001408410.1:c.1880dup NP_001395339.1:p.Gln628Profs frameshift NM_001408411.1:c.1877dup NP_001395340.1:p.Gln627Profs frameshift NM_001408412.1:c.1874dup NP_001395341.1:p.Gln626Profs frameshift NM_001408413.1:c.1874dup NP_001395342.1:p.Gln626Profs frameshift NM_001408414.1:c.1874dup NP_001395343.1:p.Gln626Profs frameshift NM_001408415.1:c.1874dup NP_001395344.1:p.Gln626Profs frameshift NM_001408416.1:c.1874dup NP_001395345.1:p.Gln626Profs frameshift NM_001408418.1:c.1838dup NP_001395347.1:p.Gln614Profs frameshift NM_001408419.1:c.1838dup NP_001395348.1:p.Gln614Profs frameshift NM_001408420.1:c.1838dup NP_001395349.1:p.Gln614Profs frameshift NM_001408421.1:c.1835dup NP_001395350.1:p.Gln613Profs frameshift NM_001408422.1:c.1835dup NP_001395351.1:p.Gln613Profs frameshift NM_001408423.1:c.1835dup NP_001395352.1:p.Gln613Profs frameshift NM_001408424.1:c.1835dup NP_001395353.1:p.Gln613Profs frameshift NM_001408425.1:c.1832dup NP_001395354.1:p.Gln612Profs frameshift NM_001408426.1:c.1832dup NP_001395355.1:p.Gln612Profs frameshift NM_001408427.1:c.1832dup NP_001395356.1:p.Gln612Profs frameshift NM_001408428.1:c.1832dup NP_001395357.1:p.Gln612Profs frameshift NM_001408429.1:c.1832dup NP_001395358.1:p.Gln612Profs frameshift NM_001408430.1:c.1832dup NP_001395359.1:p.Gln612Profs frameshift NM_001408431.1:c.1832dup NP_001395360.1:p.Gln612Profs frameshift NM_001408432.1:c.1829dup NP_001395361.1:p.Gln611Profs frameshift NM_001408433.1:c.1829dup NP_001395362.1:p.Gln611Profs frameshift NM_001408434.1:c.1829dup NP_001395363.1:p.Gln611Profs frameshift NM_001408435.1:c.1829dup NP_001395364.1:p.Gln611Profs frameshift NM_001408436.1:c.1829dup NP_001395365.1:p.Gln611Profs frameshift NM_001408437.1:c.1829dup NP_001395366.1:p.Gln611Profs frameshift NM_001408438.1:c.1829dup NP_001395367.1:p.Gln611Profs frameshift NM_001408439.1:c.1829dup NP_001395368.1:p.Gln611Profs frameshift NM_001408440.1:c.1829dup NP_001395369.1:p.Gln611Profs frameshift NM_001408441.1:c.1829dup NP_001395370.1:p.Gln611Profs frameshift NM_001408442.1:c.1829dup NP_001395371.1:p.Gln611Profs frameshift NM_001408443.1:c.1829dup NP_001395372.1:p.Gln611Profs frameshift NM_001408444.1:c.1829dup NP_001395373.1:p.Gln611Profs frameshift NM_001408445.1:c.1826dup NP_001395374.1:p.Gln610Profs frameshift NM_001408446.1:c.1826dup NP_001395375.1:p.Gln610Profs frameshift NM_001408447.1:c.1826dup NP_001395376.1:p.Gln610Profs frameshift NM_001408448.1:c.1826dup NP_001395377.1:p.Gln610Profs frameshift NM_001408450.1:c.1826dup NP_001395379.1:p.Gln610Profs frameshift NM_001408451.1:c.1820dup NP_001395380.1:p.Gln608Profs frameshift NM_001408452.1:c.1814dup NP_001395381.1:p.Gln606Profs frameshift NM_001408453.1:c.1814dup NP_001395382.1:p.Gln606Profs frameshift NM_001408454.1:c.1814dup NP_001395383.1:p.Gln606Profs frameshift NM_001408455.1:c.1814dup NP_001395384.1:p.Gln606Profs frameshift NM_001408456.1:c.1814dup NP_001395385.1:p.Gln606Profs frameshift NM_001408457.1:c.1814dup NP_001395386.1:p.Gln606Profs frameshift NM_001408458.1:c.1811dup NP_001395387.1:p.Gln605Profs frameshift NM_001408459.1:c.1811dup NP_001395388.1:p.Gln605Profs frameshift NM_001408460.1:c.1811dup NP_001395389.1:p.Gln605Profs frameshift NM_001408461.1:c.1811dup NP_001395390.1:p.Gln605Profs frameshift NM_001408462.1:c.1811dup NP_001395391.1:p.Gln605Profs frameshift NM_001408463.1:c.1811dup NP_001395392.1:p.Gln605Profs frameshift NM_001408464.1:c.1811dup NP_001395393.1:p.Gln605Profs frameshift NM_001408465.1:c.1811dup NP_001395394.1:p.Gln605Profs frameshift NM_001408466.1:c.1811dup NP_001395395.1:p.Gln605Profs frameshift NM_001408467.1:c.1811dup NP_001395396.1:p.Gln605Profs frameshift NM_001408468.1:c.1808dup NP_001395397.1:p.Gln604Profs frameshift NM_001408469.1:c.1808dup NP_001395398.1:p.Gln604Profs frameshift NM_001408470.1:c.1808dup NP_001395399.1:p.Gln604Profs frameshift NM_001408472.1:c.1952dup NP_001395401.1:p.Gln652Profs frameshift NM_001408473.1:c.1949dup NP_001395402.1:p.Gln651Profs frameshift NM_001408474.1:c.1754dup NP_001395403.1:p.Gln586Profs frameshift NM_001408475.1:c.1751dup NP_001395404.1:p.Gln585Profs frameshift NM_001408476.1:c.1751dup NP_001395405.1:p.Gln585Profs frameshift NM_001408478.1:c.1745dup NP_001395407.1:p.Gln583Profs frameshift NM_001408479.1:c.1745dup NP_001395408.1:p.Gln583Profs frameshift NM_001408480.1:c.1745dup NP_001395409.1:p.Gln583Profs frameshift NM_001408481.1:c.1742dup NP_001395410.1:p.Gln582Profs frameshift NM_001408482.1:c.1742dup NP_001395411.1:p.Gln582Profs frameshift NM_001408483.1:c.1742dup NP_001395412.1:p.Gln582Profs frameshift NM_001408484.1:c.1742dup NP_001395413.1:p.Gln582Profs frameshift NM_001408485.1:c.1742dup NP_001395414.1:p.Gln582Profs frameshift NM_001408489.1:c.1742dup NP_001395418.1:p.Gln582Profs frameshift NM_001408490.1:c.1742dup NP_001395419.1:p.Gln582Profs frameshift NM_001408491.1:c.1742dup NP_001395420.1:p.Gln582Profs frameshift NM_001408492.1:c.1739dup NP_001395421.1:p.Gln581Profs frameshift NM_001408493.1:c.1739dup NP_001395422.1:p.Gln581Profs frameshift NM_001408494.1:c.1715dup NP_001395423.1:p.Gln573Profs frameshift NM_001408495.1:c.1709dup NP_001395424.1:p.Gln571Profs frameshift NM_001408496.1:c.1691dup NP_001395425.1:p.Gln565Profs frameshift NM_001408497.1:c.1691dup NP_001395426.1:p.Gln565Profs frameshift NM_001408498.1:c.1691dup NP_001395427.1:p.Gln565Profs frameshift NM_001408499.1:c.1691dup NP_001395428.1:p.Gln565Profs frameshift NM_001408500.1:c.1691dup NP_001395429.1:p.Gln565Profs frameshift NM_001408501.1:c.1691dup NP_001395430.1:p.Gln565Profs frameshift NM_001408502.1:c.1688dup NP_001395431.1:p.Gln564Profs frameshift NM_001408503.1:c.1688dup NP_001395432.1:p.Gln564Profs frameshift NM_001408504.1:c.1688dup NP_001395433.1:p.Gln564Profs frameshift NM_001408505.1:c.1685dup NP_001395434.1:p.Gln563Profs frameshift NM_001408506.1:c.1628dup NP_001395435.1:p.Gln544Profs frameshift NM_001408507.1:c.1625dup NP_001395436.1:p.Gln543Profs frameshift NM_001408508.1:c.1616dup NP_001395437.1:p.Gln540Profs frameshift NM_001408509.1:c.1613dup NP_001395438.1:p.Gln539Profs frameshift NM_001408510.1:c.1574dup NP_001395439.1:p.Gln526Profs frameshift NM_001408511.1:c.1571dup NP_001395440.1:p.Gln525Profs frameshift NM_001408512.1:c.1451dup NP_001395441.1:p.Gln485Profs frameshift NM_001408513.1:c.1424dup NP_001395442.1:p.Gln476Profs frameshift NM_001408514.1:c.1028dup NP_001395443.1:p.Gln344Profs frameshift NM_007294.3:c.5266dupC frameshift NM_007297.4:c.5125dup NP_009228.2:p.Gln1709fs frameshift NM_007298.4:c.1952dup NP_009229.2:p.Gln652Profs frameshift NM_007299.4:c.1954dup NP_009230.2:p.Gln652fs frameshift NM_007300.4:c.5329dup NP_009231.2:p.Gln1777fs frameshift NM_007304.2:c.1952dup NP_009235.2:p.Gln652Profs frameshift NR_027676.2:n.5443dup non-coding transcript variant NC_000017.11:g.43057065dup NC_000017.10:g.41209082dup NG_005905.2:g.160921dup LRG_292:g.160921dup LRG_292t1:c.5264dup LRG_292p1:p.Gln1756Profs U14680.1:c.5263_5264insC U14680.1:n.5382_5383insC - Protein change
- Q1756fs, Q1777fs, Q652fs, Q1709fs
- Other names
-
5382_5383insC
p.Gln1756ProfsX74
NP_009225.1:p.Gln1756ProfsTer74
5382insC
5384insC
5385insC
5383insC
- Canonical SPDI
- NC_000017.11:43057062:GGG:GGGG
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
functional variant; Sequence Ontology [ SO:0001536]
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13050 | 14856 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (39) |
reviewed by expert panel
|
Apr 22, 2016 | RCV000019246.70 | |
|
Pancreatic cancer, susceptibility to
|
risk factor (1) |
no assertion criteria provided
|
Oct 15, 2008 | RCV000019247.13 |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Sep 30, 2024 | RCV000056287.25 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Mar 20, 2023 | RCV000131328.20 | |
| Pathogenic (1) |
criteria provided, single submitter
|
- | RCV000412924.9 | |
| Pathogenic (9) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV000119097.45 | |
| Pathogenic (2) |
criteria provided, single submitter
|
May 29, 2014 | RCV000415060.12 | |
| Pathogenic (16) |
criteria provided, multiple submitters, no conflicts
|
Jul 31, 2024 | RCV000258962.62 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jul 21, 2017 | RCV000495973.9 | |
| Pathogenic (3) |
criteria provided, single submitter
|
Mar 24, 2023 | RCV000735471.14 | |
| Uncertain significance (1) |
no assertion criteria provided
|
- | RCV001353680.9 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Nov 22, 2021 | RCV002504809.8 | |
| Pathogenic (1) |
no assertion criteria provided
|
Feb 21, 2023 | RCV003128129.8 | |
|
BRCA1-related disorder
|
Pathogenic (1) |
no assertion criteria provided
|
Jun 26, 2024 | RCV004554607.2 |
| click to load more click to collapse | ||||
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Apr 22, 2016)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000282341.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
Pathogenic
(Nov 03, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000195938.1
First in ClinVar: May 06, 2016 Last updated: May 06, 2016 |
Tissue: Blood
|
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: research
|
Breast Cancer
Affected status: yes
Allele origin:
germline
|
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center
Accession: SCV000492476.1
First in ClinVar: Jan 09, 2017 Last updated: Jan 09, 2017 |
|
|
|
Pathogenic
(May 29, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Ovarian neoplasm
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000493028.1
First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017 |
|
|
|
Pathogenic
(Feb 23, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Baylor Genetics
Accession: SCV000540940.1
First in ClinVar: Dec 17, 2016 Last updated: Dec 17, 2016 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Dec 10, 2015)
|
criteria provided, single submitter
Method: research
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: CSER-HudsonAlpha
Accession: SCV000584072.1 First in ClinVar: Apr 22, 2017 Last updated: Apr 22, 2017 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Oct 10, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743374.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Pathogenic
(Jun 03, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001368385.2
First in ClinVar: Jul 06, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1.
|
|
|
Pathogenic
(Apr 02, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499705.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
|
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Biomedical Genomics and Oncogenetics Laboratory, Institut Pasteur de Tunis, University Tunis El Manar
Accession: SCV001519673.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Number of individuals with the variant: 3
Age: 27-36 years
Sex: female
Geographic origin: Tunisia
|
|
|
Pathogenic
(Jan 09, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
GeneKor MSA
Accession: SCV000296781.5
First in ClinVar: Jul 01, 2016 Last updated: Oct 02, 2021 |
Comment:
This mutation is an insertion of one nucleotide (cytosine), resulting in a frameshift and the creation of a novel translational termination codon after 74 amino … (more)
This mutation is an insertion of one nucleotide (cytosine), resulting in a frameshift and the creation of a novel translational termination codon after 74 amino acid residues. The protein product thus produced is truncated and non-functional. This mutation has been described in the international bibliography (http://research.nhgri.nih.gov/projects/bic) and has been shown to be a founder mutation in a number of ethnic groups (PMID: 12142080). This mutation has been described in the mutation database ClinVar (Variation ID:17677). (less)
|
|
|
Pathogenic
(Mar 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
DASA
Accession: SCV002107076.2
First in ClinVar: Mar 28, 2022 Last updated: Apr 02, 2022 |
Comment:
The c.5266dup;p.(Gln1756Profs*74) is a null frameshift variant (NMD) in the BRCA1 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a … (more)
The c.5266dup;p.(Gln1756Profs*74) is a null frameshift variant (NMD) in the BRCA1 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevant exon to the transcript - PVS1_strong. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 17677; PMID: 15994883; PMID: 22430266) - PS4. The variant is present at low allele frequencies population databases (rs80357906 – gnomAD 0.001803%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 3
Sex: female
Geographic origin: Brazil
|
|
|
Pathogenic
(Sep 06, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002581822.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PS4, PP1_MOD
|
Number of individuals with the variant: 18
Sex: female
|
|
|
Pathogenic
(Aug 04, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Human Genetics Bochum, Ruhr University Bochum
Accession: SCV002758575.1
First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022 |
Comment:
ACMG criteria used to clasify this variant: PVS1, PM2, PS4
|
|
|
Pathogenic
(Oct 02, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000326231.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
|
|
Pathogenic
(Dec 13, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Accession: SCV002512516.2
First in ClinVar: May 21, 2022 Last updated: Dec 17, 2022 |
Comment:
ACMG classification criteria: PVS1 very strong, PS3 supporting, PS4 strong, PP1 strong
Geographic origin: Brazil
|
|
|
Pathogenic
(Nov 22, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Breast-ovarian cancer, familial, susceptibility to, 1 Pancreatic cancer, susceptibility to, 4 Fanconi anemia, complementation group S
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002813806.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Pathogenic
(Dec 09, 2022)
|
criteria provided, single submitter
Method: research
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: no
Allele origin:
germline
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV002762800.2
First in ClinVar: Dec 17, 2022 Last updated: Feb 25, 2023 |
Comment:
PVS1, PS4_STR, BS1
|
|
|
Pathogenic
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002009425.3
First in ClinVar: Oct 30, 2021 Last updated: Jul 16, 2023 |
|
|
|
Pathogenic
(Oct 05, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002058051.2
First in ClinVar: Jan 15, 2022 Last updated: Feb 20, 2024 |
Comment:
The BRCA1 c.5266dup; p.Gln1756ProfsTer74 variant, also known as 5382insC, has been described in individuals and families with hereditary breast and ovarian cancer, peritoneal cancer, and … (more)
The BRCA1 c.5266dup; p.Gln1756ProfsTer74 variant, also known as 5382insC, has been described in individuals and families with hereditary breast and ovarian cancer, peritoneal cancer, and pancreatic cancer and is a known pathogenic founder variant (Bogdanova 2010, Elsakov 2010, Heidemann 2012, Simard 1994, Uglanitsa 2010, Zhang 2011). This variant is reported as pathogenic in ClinVar (Variation ID: 17677). It is found in the general population with an overall allele frequency of 0.02% (51/282892 alleles) in the Genome Aggregation Database. This variant causes a frameshift by duplicating a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. [**Use the AJ BRCA template under BRCA NGS, OR Make sure to add the AJ recommendations from that template "If this individual is of Ashkenazi Jewish ancestry…"**] References: Bogdanova NV et al. High frequency and allele-specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus. Clin Genet. 2010 78(4):364-72. PMID: 20569256. Elsakov P et al. The contribution of founder mutations in BRCA1 to breast and ovarian cancer in Lithuania. Clin Genet. 2010 78(4):373-6. PMID: 20345474. Heidemann S et al. Double heterozygosity for mutations in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management. Breast Cancer Res Treat. 2012 134(3):1229-39. PMID: 22535016. Simard J et al. Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families. Nat Genet. 1994 8(4):392-8. PMID: 7894492. Uglanitsa N et al. The contribution of founder mutations in BRCA1 to breast cancer in Belarus. Clin Genet. 2010 78(4):377-80. PMID: 20507347. Zhang S et al. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol Oncol. 2011 121(2):353-7. PMID: 21324516. (less)
|
|
|
Pathogenic
(Mar 17, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004212667.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Jul 01, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Medical Genetics, Oslo University Hospital
Accession: SCV000564336.1
First in ClinVar: Apr 22, 2017 Last updated: Apr 22, 2017 |
Number of individuals with the variant: 30
|
|
|
Pathogenic
(Feb 14, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome(HBOC)
Affected status: unknown
Allele origin:
germline
|
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV000576438.1
First in ClinVar: Apr 16, 2017 Last updated: Apr 16, 2017 |
|
|
|
Pathogenic
(Jan 01, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Genologica Medica
Additional submitter:
Servicio Andaluz de Salud, Hospital Universitario Virgen de la Victoria
Accession: SCV000577937.1
First in ClinVar: Apr 22, 2017 Last updated: Apr 22, 2017 |
Family history: yes
Ethnicity/Population group: Causasians
Geographic origin: Spain
Tissue: Blood
Secondary finding: no
|
|
|
Pathogenic
(Jul 21, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
604370
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Bioinformatics dept., Datar Cancer Genetics Limited, India
Accession: SCV000584019.1
First in ClinVar: Jul 29, 2017 Last updated: Jul 29, 2017 |
Sex: female
|
|
|
Pathogenic
(Feb 02, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000219263.2 First in ClinVar: Mar 29, 2015 Last updated: Dec 02, 2017 |
|
|
|
Pathogenic
(Sep 21, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744589.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Pathogenic
(May 25, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV000839893.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
The c.5266dup (p.Gln1756Profs*74) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 7894492, 26718727, 20569256, 21503673, 23232912, … (more)
The c.5266dup (p.Gln1756Profs*74) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 7894492, 26718727, 20569256, 21503673, 23232912, 26666763, 22430266, 19359128, 20730485, 22032251, 21324516, among others, referred as 5382C in some publications], pancreatic cancer [PMID 24737347, 26440929] and prostate cancer [PMID 27433846 ]. This variant is a founder mutation in the Ashkenazi Jewish population and is found with a high prevalence in Poland and Eastern Europe [PMID 20569256, 20345474, 20507347]. The estimated risk for carriers of this variant was 89% for breast cancer and 42% for ovarian cancer by age 70 [PMID 22430266]. This one bp duplication in exon 19 results in a frameshift and the creation of a premature stop codon. This variant is thus predicted to result in a loss of function of the protein. This variant has been detected in 19 individuals from the ExAC database (http://exac.broadinstitute.org/variant/17-41209079-T-TG). This variant thus classified as pathogenic. (less)
|
|
|
Pathogenic
(Nov 07, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000226938.4
First in ClinVar: Jun 28, 2015 Last updated: Jul 31, 2019 |
Number of individuals with the variant: 2
Sex: mixed
|
|
|
Pathogenic
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001140476.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
|
|
|
Pathogenic
(-)
|
criteria provided, single submitter
Method: research
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Institute of Genomics, University of Tartu
Accession: SCV001430693.1
First in ClinVar: Aug 24, 2020 Last updated: Aug 24, 2020 |
Number of individuals with the variant: 11
Sex: mixed
|
|
|
Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447116.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Neuroblastoma (present)
Sex: female
|
|
|
Pathogenic
(Sep 18, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001449581.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 11
|
|
|
Pathogenic
(Feb 12, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000209886.7
First in ClinVar: Feb 24, 2015 Last updated: Jun 10, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Truncating variants in this gene … (more)
Frameshift variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5382insC or 5385insC; This variant is associated with the following publications: (PMID: 25859162, 25849179, 27160020, 26843898, 26852130, 26833046, 27025497, 27062684, 26681312, 29790872, 26440929, 30067863, 31336956, 32854451, 24372583, 21119707, 26656232, 26083025, 25476495, 24528374, 25195694, 22032251, 7894492, 16168118, 27223485, 26779294, 27433846, 26666763, 26718727, 29478780, 27425403, 22009639, 20569256, 21503673, 23232912, 20345474, 22430266, 29335925, 28285342, 22535016, 29339979, 23954390, 29433453, 29335924, 29492181, 21834074, 24737347, 19359128, 27914478, 28324225, 22666503, 27989354, 29907814, 20730485, 28091860, 28503720, 26556299, 10464624, 28423363, 20507347, 22006311, 25980754, 21324516, 29310832, 30333958, 30159786, 29161300, 30606148, 30152102, 28049106, 28111427, 30186769, 29961768, 30322717, 31090900, 31159747, 30113427, 23199084, 8841191, 30676620, 30489631, 31454914, 12771565, 31528241, 27741520, 29625052, 26689913, 32058061, 31447099, 32039725) (less)
|
|
|
Pathogenic
(Nov 16, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002025907.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Geographic origin: South Africa
Testing laboratory: National Health Laboratory Service (NHLS)
|
|
|
Pathogenic
(Oct 29, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV002051788.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
Comment:
This BRCA1 variant (rs80357906) is rare (<0.1%) in a large population dataset (gnomAD: 51/282892 total alleles, 0.018%, no homozygotes) and has been reported in ClinVar. … (more)
This BRCA1 variant (rs80357906) is rare (<0.1%) in a large population dataset (gnomAD: 51/282892 total alleles, 0.018%, no homozygotes) and has been reported in ClinVar. This frameshift variant results in a premature stop codon in exon 19 of 23 likely leading to nonsense-mediated decay and lack of protein production. This variant, also known as 5382insC and 5385insC in the literature, is a common cause of breast and ovarian cancer in the Ashkenazi Jewish population and has been reported in individuals from other ethnicities. This variant has been associated with a 67% to 89% risk of breast cancer by age 70, and a 33% to 42% risk of ovarian cancer by age 70. This variant was also identified in the patient's mother (JHG1740-2). We consider c.5266dupC to be pathogenic. (less)
|
|
|
Pathogenic
(Apr 22, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000494397.2
First in ClinVar: Feb 04, 2017 Last updated: Dec 11, 2022 |
Comment:
Variant summary: The BRCA1 c.5266dupC variant results in a frameshift, which alters the protein's amino acid sequence beginning at position 1756 and leads to a … (more)
Variant summary: The BRCA1 c.5266dupC variant results in a frameshift, which alters the protein's amino acid sequence beginning at position 1756 and leads to a premature termination codon 73 amino acids downstream. It is predicted to cause a truncated or absent BRCA1 protein due to non-sense meditated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (such as c.5387C>A/p.Ser1796X, c.5417delC/Pro1806fsX28, etc). Mutation Taster predicts a damaging outcome for this variant, and functional studies have shown HR activity is significantly impaired by this variant (Bouwman_BRCA1_Cancer Discovery_2013). BRCA1 c.5266dupC was found in 19/121412 control chromosomes at a frequency of 0.0001565, which does not exceed maximal expected frequency of a pathogenic BRCA1 allele (0.0010005). The variant has been cited in hundreds of HBOC patients and is reported as a known common founder mutation in the literature. Additionally, this variant has been classified by multiple clinical labs and databases as pathogenic. Taken together, this variant was classified as disease variant/pathogenic. (less)
|
|
|
Pathogenic
(Aug 23, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556792.2
First in ClinVar: Aug 08, 2022 Last updated: Dec 17, 2022 |
|
|
|
Pathogenic
(Jul 07, 2014)
|
criteria provided, single submitter
Method: literature only
|
Breast-ovarian cancer, familial 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000220482.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
|
|
|
Pathogenic
(Jan 28, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
New York Genome Center
Accession: SCV003925393.1
First in ClinVar: May 20, 2023 Last updated: May 20, 2023 |
Comment:
The c.5266dup (p.Gln1756ProfsTer74) variant identified in the BRCA1 gene is the duplication of a single nucleotide resulting in a frameshift at amino acid 1756/1863 (exon … (more)
The c.5266dup (p.Gln1756ProfsTer74) variant identified in the BRCA1 gene is the duplication of a single nucleotide resulting in a frameshift at amino acid 1756/1863 (exon 19/23). This variant is predicted to incorporate a premature termination codon at approximately 74 amino acids downstream and result in either loss-of-function via nonsense mediated decay or protein truncation. This variant is found with low frequency in gnomAD(v3.1.2) (8 heterozygotes, 0 homozygotes; allele frequency: 1.972e-5), suggesting it is not a common benign variant in the populations represented in that database. The c.5266dup (p.Gln1756ProfsTer74) variant is reported in ClinVar as Pathogenic by an expert panel (VarID: 17677), and is one of the most frequently reported pathogenic variants in the BRCA1 gene. This variant has been reported in multiple affected individuals in the literature [PMID: 21119707, 24797986, 31706072, others]. Based on the available evidence c.5266dup(p.Gln1756ProfsTer74) variant is reported as Pathogenic. (less)
Clinical Features:
Hyperlipidemia (present)
Secondary finding: yes
|
|
|
Pathogenic
(May 18, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Illumina Laboratory Services, Illumina
Accession: SCV004014748.1
First in ClinVar: Jul 22, 2023 Last updated: Jul 22, 2023 |
Comment:
The BRCA1 c.5266dup (p.Gln1756ProfsTer74) variant, also referred to as c.5382insC or c.5382_5383insC, causes a shift in the translational reading frame that is predicted to result … (more)
The BRCA1 c.5266dup (p.Gln1756ProfsTer74) variant, also referred to as c.5382insC or c.5382_5383insC, causes a shift in the translational reading frame that is predicted to result in premature termination of the protein. Loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay is expected. This variant has been previously identified in individuals with breast cancer, ovarian cancer, pancreatic cancer, and prostate cancer (PMID: 29335925; PMID: 29961768; PMID: 11802209; PMID: 29492181; PMID: 22430266). Further, this variant is one of three well-characterized founder variants in the Ashkenazi Jewish population, accounting for an estimated 26% of pathogenic variants detected in this population (GeneReviews PMID: 20301425). The highest frequency of this allele in the Genome Aggregation Database is 0.002314 in the Ashkenazi Jewish population (v2.1.1). This variant has been classified as pathogenic by >60 submitters in ClinVar, including a BRCA1 expert panel. Based on the available evidence, the c.5266dup (p.Gln1756ProfsTer74) variant is classified as pathogenic for hereditary breast and ovarian cancer. (less)
|
|
|
Pathogenic
(Jun 04, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296309.7
First in ClinVar: Jun 24, 2016 Last updated: Jan 06, 2024 |
Comment:
The BRCA1 c.5266dup (p.Gln1756Profs*74) variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. This variant … (more)
The BRCA1 c.5266dup (p.Gln1756Profs*74) variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. This variant has been reported in the published literature as a founder mutation in the Ashkenazi Jewish population and has been reported in multiple individuals and families affected with breast and/or ovarian cancer (PMIDs: 18694767 (2008), 19208665 (2009), 21119707 (2011), 30606148 (2019), 32438681 (2020), 35409996 (2022)), as well as prostate cancer (PMID: 36612302 (2023)). This variant has also been reported in affected and control individuals in a large-scale breast cancer association study (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/)). A functional study showed that this variant caused the complete loss of BRCA1 phosphopeptide binding activity (PMID: 15133502 (2004)). Based on the available information, this variant is classified as pathogenic. (less)
|
|
|
Pathogenic
(May 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000778733.3
First in ClinVar: Jun 23, 2018 Last updated: Jan 26, 2024 |
Comment:
PP5, PS4_moderate, PVS1
Number of individuals with the variant: 19
|
|
|
Pathogenic
(Jan 17, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg
Accession: SCV004231809.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
This variant has been identified by standard clinical testing. female patient with metastatic breast cancer Selected ACMG criteria: Pathogenic (I):PP5;PS4;PVS1
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Sep 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003811722.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Mar 24, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Study: Canadian Open Genetics Repository
Accession: SCV000901129.3 First in ClinVar: May 06, 2019 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000076906.17
First in ClinVar: Jul 03, 2013 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln1756Profs*74) in the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Gln1756Profs*74) in the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 108 amino acid(s) of the BRCA1 protein. This variant is present in population databases (rs397507247, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer. It is commonly reported in individuals of Ashkenazi Jewish ancestry (PMID: 9042909, 22185575, 22430266). This variant is also known as 5382insC and 5385insC. ClinVar contains an entry for this variant (Variation ID: 17677). This variant has been associated with a 67% to 89% risk of breast cancer by age 70, and a 33% to 42% risk of ovarian cancer by age 70 (PMID: 15994883, 22430266). This variant disrupts a region of the BRCA1 protein in which other variant(s) (Deletion (Exon 23)) have been determined to be pathogenic (PMID: 18431737, 24825132, 25428789; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Mar 20, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000292125.4
First in ClinVar: Jul 08, 2016 Last updated: Feb 14, 2024 |
Comment:
This variant (also known as 5382insC and 5385insC) inserts 1 nucleotide in exon 19 of the BRCA1 gene, causing a frameshift and a premature translational … (more)
This variant (also known as 5382insC and 5385insC) inserts 1 nucleotide in exon 19 of the BRCA1 gene, causing a frameshift and a premature translational stop signal in the last exon. The mutant transcript is expected to escape nonsense-mediated decay and be expressed as a truncated protein that lacks the C-terminal BRCT domain. Experimental studies have shown that variant impacts BRCA1 function in homology-directed repair and subcellular localization assays (PMID: 14729053, 23867111). This variant is a well-known founder mutation in the Ashkenazi Jewish population and occurs at 0.13-0.28% minor allele frequency (PMID: 8841191, 9145676, 11466700, 30152102). This variant has been reported in numerous individuals affected with breast and/or ovarian cancer (PMID: 7545954, 7894492, 8531967, 9042909, 9150153, 17922257, 18334730, 21643751, 22430266, 25418591, 29335925, 30480775, 30606148, 30975216). This variant is the most globally frequent, pathogenic BRCA1 variant and has been reported in diverse populations in Africa, America, Asia and Europe (PMID: 24312913). The risk of female breast cancer among carriers of this mutation is 67-89% by age 70, and the risk of ovarian cancer is 22-42% by age 70 (PMID: 9145676, 15994883, 22430266). A breast cancer case-control meta-analysis has reported this variant in 97/60369 cases and 11/53450 controls with an estimated OR of 7.808 (95%CI 4.185 to 14.567) (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_000440). This variant has been identified in 51/282892 chromosomes (24/10370 Ashkenazi Jewish chromosomes and 25/129200 Non-Finnish European chromosomes) in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic. (less)
|
|
|
Pathogenic
(Feb 02, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Institute of Immunology and Genetics Kaiserslautern
Accession: SCV004363615.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
ACMG Criteria: PM2_P; Variant was found in heterozygous state
Clinical Features:
Breast carcinoma (present)
|
|
|
Pathogenic
(Nov 23, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000271320.5
First in ClinVar: May 29, 2016 Last updated: Apr 20, 2024 |
Comment:
The p.Gln1756ProfsX74 variant in BRCA1 (also referred to as p.Gln1777fs) is a founder variant in the Ashkenazi Jewish population and has been reported in >1000 … (more)
The p.Gln1756ProfsX74 variant in BRCA1 (also referred to as p.Gln1777fs) is a founder variant in the Ashkenazi Jewish population and has been reported in >1000 individuals with BRCA1-associated cancers (Abeliovich 1997 PMID: 9042909, Elwad 2011 PMID: 22185575, Breast Cancer Information Core (BIC) database). This variant has also been identified in 0.2% (24/103702) Ashkenazi Jewish and 0.02% (25/129200) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1756 and leads to a premature termination codon 74 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism in hereditary breast and ovarian cancer (HBOC). Furthermore, the p.Gln1756ProfsX74 variant was classified as Pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar ID 17677). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PS4, PVS1. (less)
|
|
|
Pathogenic
(May 24, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000186302.9
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The c.5266dupC (p.Q1756Pfs*74) alteration, located in exon 19 (coding exon 18) of the BRCA1 gene, consists of a duplication of C at position 5266, causing … (more)
The c.5266dupC (p.Q1756Pfs*74) alteration, located in exon 19 (coding exon 18) of the BRCA1 gene, consists of a duplication of C at position 5266, causing a translational frameshift with a predicted alternate stop codon after amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This alteration is one of three well-characterized Ashkenazi Jewish founder mutations, with an overall carrier frequency of nearly 0.5% in this population, but has also been shown to occur at high frequency in many other European populations (Hartge, 1999; Hamel, 2011; Kluz, 2018). Cumulative female breast cancer and ovarian cancer risks (by age 70) associated with this specific mutation have been estimated in the literature at 67% (range: 36-83%) and 33% (range: 8-50%), respectively (Antoniou, 2005). Of note, this mutation is also designated as 5382insC and 5385insC in the published literature. Based on the available evidence, this alteration is classified as pathogenic. (less)
|
|
|
Pathogenic
(Mar 11, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Clinical Genomics Laboratory, Washington University in St. Louis
Accession: SCV005045105.1
First in ClinVar: May 26, 2024 Last updated: May 26, 2024 |
Comment:
The BRCA1 c.5266dup (p.Gln1756Profs*74) variant is one of the most common variants reported in Central and Eastern European families with high risk of breast and/or … (more)
The BRCA1 c.5266dup (p.Gln1756Profs*74) variant is one of the most common variants reported in Central and Eastern European families with high risk of breast and/or ovarian cancer (Janavicius R, PMID: 23199084). This variant causes a frameshift by inserting one nucleotide, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. This variant has been reported in the ClinVar database as a germline pathogenic variant by 10 submitters. Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as pathogenic. (less)
|
|
|
Pathogenic
(May 27, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Accession: SCV005045968.1
First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024 |
Comment:
PVS1; PM5_PTC_Strong
|
|
|
Pathogenic
(Jul 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002550948.7
First in ClinVar: Jul 23, 2022 Last updated: Aug 04, 2024 |
|
|
|
Pathogenic
(Mar 18, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005199697.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
|
|
|
Pathogenic
(Sep 30, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV003925649.4
First in ClinVar: May 20, 2023 Last updated: Oct 13, 2024 |
Comment:
Criteria applied: PVS1,PS4,PM5_STR
Clinical Features:
Family history of cancer (present)
Sex: female
|
|
|
Pathogenic
(Jul 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247342.23
First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024 |
Comment:
BRCA1: PVS1, PS4:Moderate
Number of individuals with the variant: 23
|
|
|
Pathogenic
(Oct 08, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001251420.13
First in ClinVar: May 31, 2020 Last updated: Nov 17, 2024 |
Clinical Features:
Breast carcinoma (present)
Sex: female
|
|
|
Pathogenic
(Jul 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV005399566.1
First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Fanconi anaemia, complementation group S (MIM#617883), susceptibility to breast and ovarian cancer (MIM#604370) and susceptibility to pancreatic cancer (MIM#614320). (I) 0108 - This gene is associated with both recessive and dominant disease. Susceptibility to breast and ovarian cancer follows an autosomal dominant inheritance pattern, while Fanconi anaemia is inherited in an autosomal recessive pattern (OMIM). (I) 0112 - The condition associated with this gene has incomplete penetrance. The highest estimate for cancer risk in carriers of pathogenic variants is 80% by the age of 70 years (PMID: 30551077). (I) 0205 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with less than 1/3 of the protein sequence affected. (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 (v2 & v3: 53 heterozygotes, 0 homozygotes). (SP) 0701 - Other variants located downstream and predicted to result in a truncated protein comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0801 - This variant has very strong previous evidence of pathogenicity in unrelated individuals. It is regarded as pathogenic by multiple diagnostic laboratories including expert panel ENIGMA and associated with susceptibility to breast cancer (ClinVar). In addition, it is a founder mutation in Ashkenazi Jewish (GeneReviews). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
|
|
|
Pathogenic
(Jan 22, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Accession: SCV005402393.1
First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024 |
Comment:
The BRCA1 c.5266dup (p.Gln1756ProfsTer74) change duplicates one nucleotide to cause a frameshift and the creation of a premature stop codon. This change is predicted to … (more)
The BRCA1 c.5266dup (p.Gln1756ProfsTer74) change duplicates one nucleotide to cause a frameshift and the creation of a premature stop codon. This change is predicted to cause protein truncation. This variant, which is also known as c.5382insC in published literature, has been reported in several individuals with BRCA1-related cancers (PMID: 7894492, 9634504, 10739756, 22666503, 24737347, 26440929, 27433846, 32058061) and is an Ashkenazi Jewish founder mutation (PMID: 30152102). In summary, this variant meets criteria to be classified as pathogenic. (less)
|
|
|
Pathogenic
(Oct 15, 2008)
|
no assertion criteria provided
Method: literature only
|
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1
Affected status: not provided
Allele origin:
unknown
|
OMIM
Accession: SCV000039534.4
First in ClinVar: Apr 04, 2013 Last updated: Apr 09, 2018 |
Comment on evidence:
Breast-Ovarian Cancer Susceptibility Simard et al. (1994) studied 30 Canadian families with breast and/or ovarian cancer (604370) for germline mutations in the coding region of … (more)
Breast-Ovarian Cancer Susceptibility Simard et al. (1994) studied 30 Canadian families with breast and/or ovarian cancer (604370) for germline mutations in the coding region of the BRCA1 candidate gene. They identified a 1-bp (C) insertion at position 5382 in exon 20, changing the reading frame of the mRNA and causing a premature termination codon at position 1829 in exon 24. This mutation was detected in the index case of 4 Canadian families. In 1 of these families, 10 cases of cancer appeared in a single large sibship, including 3 cases of breast cancer, 2 ovarian cancers, 2 leukemias, 2 pancreatic cancers, and 1 prostate cancer. A case of leukemia and a case of Hodgkin disease were seen in more recent generations. In the 4 families with the 5382insC mutation, there were 14 cases of breast cancer and 5 cases of ovarian cancer. Gayther et al. (1997) found that the 5382insC and 4153delA (113705.0030) mutations in the BRCA1 gene may account for 86% of cases of familial ovarian cancer in Russia. Gorski et al. (2000) found that 5382insC is a founder mutation in Polish families with breast-ovarian cancer, accounting for 51% of identified mutations. They studied 66 families in which at least 3 related females were affected with breast or ovarian cancer and at least 1 of these 3 had been diagnosed with cancer before the age of 50. Mutations were found in 35 (53%) of the 66 families; 18 of the families carried the 5382insC mutation. De Los Rios et al. (2001) reported findings in Canadian families suggesting that most of the mutation-carrying families of Polish ancestry have the BRCA1 5382insC mutation. Porhanova et al. (2008) reported a 52-year-old Russian woman with ovarian cancer who was found to be compound heterozygous for the 5382inC mutation and a common Slavic mutation in the NBN gene (602667.0001). Investigation of the ovarian cancer tissue showed somatic loss of heterozygosity for NBN, but retention of heterozygosity for BRCA1. The patient did not have a particularly severe cancer-prone phenotype, and her parents did not have cancer, although 3 sibs developed cancer as adults. Porhanova et al. (2008) commented that haploinsufficiency of the BRCA1 gene may contribute to cancer progression without somatic changes. Pancreatic Cancer Susceptibility Al-Sukhni et al. (2008) found loss of heterozygosity at the BRCA1 locus in pancreatic tumor DNA from 5 (71%) of 7 patients with pancreatic cancer (PNCA4; 614320) who carried a heterozygous germline BRCA1 mutation. Three patients carried the 5382insC mutation. In contrast, only 1 (11%) of 9 patients with sporadic pancreatic cancer and no germline BRCA1 mutations showed LOH at the BRCA1 locus. Al-Sukhni et al. (2008) concluded that BRCA1 germline mutations likely predispose to the development of pancreatic cancer, and suggested that individuals with these mutations be considered for pancreatic cancer-screening programs. (less)
|
|
|
risk factor
(Oct 15, 2008)
|
no assertion criteria provided
Method: literature only
|
PANCREATIC CANCER, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin:
unknown
|
OMIM
Accession: SCV000053476.4
First in ClinVar: Apr 04, 2013 Last updated: Dec 15, 2018 |
Comment on evidence:
Breast-Ovarian Cancer Susceptibility Simard et al. (1994) studied 30 Canadian families with breast and/or ovarian cancer (604370) for germline mutations in the coding region of … (more)
Breast-Ovarian Cancer Susceptibility Simard et al. (1994) studied 30 Canadian families with breast and/or ovarian cancer (604370) for germline mutations in the coding region of the BRCA1 candidate gene. They identified a 1-bp (C) insertion at position 5382 in exon 20, changing the reading frame of the mRNA and causing a premature termination codon at position 1829 in exon 24. This mutation was detected in the index case of 4 Canadian families. In 1 of these families, 10 cases of cancer appeared in a single large sibship, including 3 cases of breast cancer, 2 ovarian cancers, 2 leukemias, 2 pancreatic cancers, and 1 prostate cancer. A case of leukemia and a case of Hodgkin disease were seen in more recent generations. In the 4 families with the 5382insC mutation, there were 14 cases of breast cancer and 5 cases of ovarian cancer. Gayther et al. (1997) found that the 5382insC and 4153delA (113705.0030) mutations in the BRCA1 gene may account for 86% of cases of familial ovarian cancer in Russia. Gorski et al. (2000) found that 5382insC is a founder mutation in Polish families with breast-ovarian cancer, accounting for 51% of identified mutations. They studied 66 families in which at least 3 related females were affected with breast or ovarian cancer and at least 1 of these 3 had been diagnosed with cancer before the age of 50. Mutations were found in 35 (53%) of the 66 families; 18 of the families carried the 5382insC mutation. De Los Rios et al. (2001) reported findings in Canadian families suggesting that most of the mutation-carrying families of Polish ancestry have the BRCA1 5382insC mutation. Porhanova et al. (2008) reported a 52-year-old Russian woman with ovarian cancer who was found to be compound heterozygous for the 5382inC mutation and a common Slavic mutation in the NBN gene (602667.0001). Investigation of the ovarian cancer tissue showed somatic loss of heterozygosity for NBN, but retention of heterozygosity for BRCA1. The patient did not have a particularly severe cancer-prone phenotype, and her parents did not have cancer, although 3 sibs developed cancer as adults. Porhanova et al. (2008) commented that haploinsufficiency of the BRCA1 gene may contribute to cancer progression without somatic changes. Pancreatic Cancer Susceptibility Al-Sukhni et al. (2008) found loss of heterozygosity at the BRCA1 locus in pancreatic tumor DNA from 5 (71%) of 7 patients with pancreatic cancer (PNCA4; 614320) who carried a heterozygous germline BRCA1 mutation. Three patients carried the 5382insC mutation. In contrast, only 1 (11%) of 9 patients with sporadic pancreatic cancer and no germline BRCA1 mutations showed LOH at the BRCA1 locus. Al-Sukhni et al. (2008) concluded that BRCA1 germline mutations likely predispose to the development of pancreatic cancer, and suggested that individuals with these mutations be considered for pancreatic cancer-screening programs. (less)
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001906306.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
|
Pathogenic
(Jun 26, 2024)
|
no assertion criteria provided
Method: clinical testing
|
BRCA1-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000806969.4
First in ClinVar: Jun 23, 2018 Last updated: Oct 08, 2024 |
Comment:
The BRCA1 c.5266dupC variant is predicted to result in a frameshift and premature protein termination (p.Gln1756Profs*74). This variant (also described as 5382insC, 5385insC, or 5329dupC) … (more)
The BRCA1 c.5266dupC variant is predicted to result in a frameshift and premature protein termination (p.Gln1756Profs*74). This variant (also described as 5382insC, 5385insC, or 5329dupC) has been reported in multiple individuals with autosomal dominant hereditary breast and ovarian cancer syndrome (HBOC) (OMIM #604370; Bogdanova et al. 2010. PubMed ID: 20569256; Alemar et al. 2016. PubMed ID: 27425403; Azzollini et al. 2016. PubMed ID: 27062684; Hamel et al. 2011. PubMed ID: 21119707). It is a founder variant in the Ashkenazi Jewish population and is reported in 0.23% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. It is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/17677/). Frameshift variants in BRCA1 are expected to be pathogenic. In summary, this variant is interpreted as pathogenic. (less)
|
|
|
Pathogenic
(Jul 24, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: unknown
Allele origin:
germline
|
Pathway Genomics
Accession: SCV000189885.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
|
|
|
Pathogenic
(Feb 11, 2015)
|
no assertion criteria provided
(clinical testing)
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, Medical University Innsbruck
Study: BRCA-Tyrol
Accession: SCV000212010.1 First in ClinVar: Mar 03, 2015 Last updated: Mar 03, 2015
Comment:
BRCA-mutation spectrum Western Austria
|
|
|
|
Pathogenic
(May 29, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline,
unknown
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145419.2
First in ClinVar: Apr 04, 2014 Last updated: Oct 11, 2015 |
Observation 1:
Number of individuals with the variant: 1108
Observation 2:
Number of individuals with the variant: 1
Geographic origin: American
Observation 3:
Number of individuals with the variant: 46
Geographic origin: Ashkenazi
Observation 4:
Number of individuals with the variant: 1
Geographic origin: Ashkenazi, Central/Eastern European
Observation 5:
Number of individuals with the variant: 4
Geographic origin: Austria
Observation 6:
Number of individuals with the variant: 2
Geographic origin: Belgium
Observation 7:
Number of individuals with the variant: 1
Geographic origin: Canada
Observation 8:
Number of individuals with the variant: 7
Geographic origin: Central/Eastern European
Observation 9:
Number of individuals with the variant: 1
Geographic origin: Danish German
Observation 10:
Number of individuals with the variant: 5
Geographic origin: Netherlands
Observation 11:
Number of individuals with the variant: 2
Geographic origin: France
Observation 12:
Number of individuals with the variant: 5
Geographic origin: Germany
Observation 13:
Number of individuals with the variant: 4
Geographic origin: Italy
Observation 14:
Number of individuals with the variant: 6
Geographic origin: Latvia
Observation 15:
Number of individuals with the variant: 1
Geographic origin: Near Eastern Mid East
Observation 16:
Number of individuals with the variant: 1
Geographic origin: Poland
Observation 17:
Number of individuals with the variant: 13
Geographic origin: Western European
Observation 18:
Number of individuals with the variant: 319
Ethnicity/Population group: Ashkenazi
Observation 19:
Number of individuals with the variant: 3
Ethnicity/Population group: Ashkenazi Jewish
Observation 20:
Number of individuals with the variant: 3
Ethnicity/Population group: Ashkenazi Jewish
Geographic origin: American
Observation 21:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi Jewish
Geographic origin: Lithuania
Observation 22:
Number of individuals with the variant: 10
Ethnicity/Population group: Ashkenazi, Central/Eastern European
Observation 23:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi, Italian
Observation 24:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi, Russian
Observation 25:
Number of individuals with the variant: 2
Ethnicity/Population group: Ashkenazi, Western European
Observation 26:
Number of individuals with the variant: 2
Ethnicity/Population group: Austrian
Geographic origin: Austria
Observation 27:
Number of individuals with the variant: 3
Ethnicity/Population group: Caucasian
Observation 28:
Number of individuals with the variant: 3
Ethnicity/Population group: Caucasian
Geographic origin: American
Observation 29:
Number of individuals with the variant: 54
Ethnicity/Population group: Caucasian
Geographic origin: Czech Republic
Observation 30:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Denmark
Observation 31:
Number of individuals with the variant: 5
Ethnicity/Population group: Caucasian
Geographic origin: Netherlands
Observation 32:
Number of individuals with the variant: 2
Ethnicity/Population group: Caucasian
Geographic origin: France
Observation 33:
Number of individuals with the variant: 9
Ethnicity/Population group: Caucasian
Geographic origin: Germany
Observation 34:
Number of individuals with the variant: 16
Ethnicity/Population group: Caucasian
Geographic origin: Italy
Observation 35:
Number of individuals with the variant: 49
Ethnicity/Population group: Central/Eastern European
Observation 36:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European, Jewish
Observation 37:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European, Latin American, Ca
Observation 38:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European, Russian
Observation 39:
Number of individuals with the variant: 1
Ethnicity/Population group: Danish
Observation 40:
Number of individuals with the variant: 1
Ethnicity/Population group: Eastern European Jewish
Observation 41:
Number of individuals with the variant: 1
Ethnicity/Population group: French Canadian, German, Scottish
Observation 42:
Number of individuals with the variant: 1
Ethnicity/Population group: French, German
Observation 43:
Number of individuals with the variant: 1
Ethnicity/Population group: German
Observation 44:
Number of individuals with the variant: 1
Ethnicity/Population group: German, Englishranian, Polish
Observation 45:
Number of individuals with the variant: 1
Ethnicity/Population group: Greek
Observation 46:
Number of individuals with the variant: 9
Ethnicity/Population group: Greek
Geographic origin: Greece
Observation 47:
Number of individuals with the variant: 1
Ethnicity/Population group: Halian Meditteranean
Observation 48:
Number of individuals with the variant: 1
Ethnicity/Population group: Irish, German
Observation 49:
Number of individuals with the variant: 1
Ethnicity/Population group: Irish, Polish
Observation 50:
Number of individuals with the variant: 1
Ethnicity/Population group: Italian
Observation 51:
Number of individuals with the variant: 9
Ethnicity/Population group: Jewish
Observation 52:
Number of individuals with the variant: 1
Ethnicity/Population group: Jewish
Geographic origin: American
Observation 53:
Number of individuals with the variant: 1
Ethnicity/Population group: Jewish
Geographic origin: Poland
Observation 54:
Number of individuals with the variant: 1
Ethnicity/Population group: Lat, Rus
Geographic origin: Latvia
Observation 55:
Number of individuals with the variant: 3
Ethnicity/Population group: Latin American, Caribbean
Observation 56:
Number of individuals with the variant: 4
Ethnicity/Population group: Latvian
Geographic origin: Latvia
Observation 57:
Number of individuals with the variant: 1
Ethnicity/Population group: Lithuanian
Observation 58:
Number of individuals with the variant: 3
Ethnicity/Population group: Native American
Observation 59:
Number of individuals with the variant: 1
Ethnicity/Population group: Near Eastern
Observation 60:
Number of individuals with the variant: 1
Ethnicity/Population group: Near Eastern, Syrian, Middle Eastern
Observation 61:
Number of individuals with the variant: 1
Ethnicity/Population group: Not Jewish
Observation 62:
Number of individuals with the variant: 2
Ethnicity/Population group: Polish
Observation 63:
Number of individuals with the variant: 1
Ethnicity/Population group: Polish
Geographic origin: France
Observation 64:
Number of individuals with the variant: 2
Ethnicity/Population group: Polish
Geographic origin: Poland
Observation 65:
Number of individuals with the variant: 1
Ethnicity/Population group: Polish, German, Englishranian
Observation 66:
Number of individuals with the variant: 1
Ethnicity/Population group: Polish, Russian
Observation 67:
Number of individuals with the variant: 1
Ethnicity/Population group: Polish, Slavic, Eastern
Observation 68:
Number of individuals with the variant: 1
Ethnicity/Population group: Rus, Englishr
Geographic origin: Latvia
Observation 69:
Number of individuals with the variant: 1
Ethnicity/Population group: Russian
Observation 70:
Number of individuals with the variant: 4
Ethnicity/Population group: Russian
Geographic origin: Latvia
Observation 71:
Number of individuals with the variant: 1
Ethnicity/Population group: Russian, Polish
Observation 72:
Number of individuals with the variant: 1
Ethnicity/Population group: Southern Italian
Geographic origin: France
Observation 73:
Number of individuals with the variant: 134
Ethnicity/Population group: Western European
Observation 74:
Number of individuals with the variant: 7
Ethnicity/Population group: Western European, Ashkenazi
Observation 75:
Number of individuals with the variant: 2
Ethnicity/Population group: Western European, Ashkenazi, Central, Eas
Observation 76:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Ashkenazi, French Canadian
Observation 77:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Ashkenazi, German, Irish
Observation 78:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Ashkenazi, Russian, Jewish
Observation 79:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Asian
Observation 80:
Number of individuals with the variant: 6
Ethnicity/Population group: Western European, Central/Eastern European
Observation 81:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Central/Eastern European, Italian, Czech, Polish
Observation 82:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Eastern Central European
Observation 83:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, German
Observation 84:
Number of individuals with the variant: 2
Ethnicity/Population group: Western European, Italian
Observation 85:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Mayan
Observation 86:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Native American
Observation 87:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Near Eastern
Observation 88:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Polish
Observation 89:
Number of individuals with the variant: 4
Ethnicity/Population group: Western Europeanan, Central/Eastern European
Observation 90:
Number of individuals with the variant: 3
Ethnicity/Population group: Western, Central/Eastern European
Observation 91:
Number of individuals with the variant: 3
Geographic origin: Germany
|
|
|
Pathogenic
(Apr 08, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000053833.5
First in ClinVar: Apr 04, 2013 Last updated: Jun 24, 2016 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare
Accession: SCV000484933.1
First in ClinVar: Dec 17, 2016 Last updated: Dec 17, 2016 |
|
|
|
Pathogenic
(Jan 31, 2014)
|
no assertion criteria provided
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587484.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733591.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Pathogenic
(Apr 27, 2018)
|
no assertion criteria provided
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
True Health Diagnostics
Accession: SCV000805234.1
First in ClinVar: Oct 21, 2017 Last updated: Oct 21, 2017 |
|
|
|
Pathogenic
(Jul 07, 2016)
|
no assertion criteria provided
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000863608.1 First in ClinVar: Dec 24, 2018 Last updated: Dec 24, 2018 |
|
|
|
Pathogenic
(Dec 01, 2018)
|
no assertion criteria provided
Method: research
|
Ovarian neoplasm
Affected status: yes
Allele origin:
germline
|
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV000923779.1
First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019 |
|
|
|
Pathogenic
(Jun 11, 2019)
|
no assertion criteria provided
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: yes
Allele origin:
germline
|
CZECANCA consortium
Accession: SCV001451781.1
First in ClinVar: Dec 26, 2020 Last updated: Dec 26, 2020 |
Number of individuals with the variant: 75
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
|
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591601.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002036964.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
|
|
|
Pathogenic
(Aug 26, 2022)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
BRCAlab, Lund University
Accession: SCV002588831.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
|
|
|
Pathogenic
(Jan 10, 2022)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002065769.3
First in ClinVar: Jan 29, 2022 Last updated: Dec 11, 2022 |
Comment:
DNA sequence analysis of the BRCA1 gene demonstrated a single base pair duplication in exon 19, c.5266dup. This pathogenic sequence change results in an amino … (more)
DNA sequence analysis of the BRCA1 gene demonstrated a single base pair duplication in exon 19, c.5266dup. This pathogenic sequence change results in an amino acid frameshift and creates a premature stop codon 74 amino acids downstream of the change, p.Gln1756Profs*74. This pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated BRCA1 protein with potentially abnormal function. This sequence change has been described in the gnomAD database with a frequency of 0.23% in the Ashkenazi Jewish subpopulation (dbSNP rs1217805587). This pathogenic sequence change is a well-described pathogenic BRCA1 variant and a known founder mutation in the Ashkenazi Jewish population reported in multiple individuals with hereditary breast and ovarian cancer syndrome (PMID: 12473589, 15131399, 9042909, 22430266, 24764757, 26976419). The c.5266dup sequence change is also referred to as 5382insC in the scientific literature (less)
|
|
|
Pathogenic
(Feb 21, 2023)
|
no assertion criteria provided
Method: clinical testing
|
Endometrial carcinoma
Affected status: yes
Allele origin:
germline
|
CZECANCA consortium
Accession: SCV003804343.1
First in ClinVar: Feb 25, 2023 Last updated: Feb 25, 2023 |
Number of individuals with the variant: 4
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: research
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Medical Genetics, Medical University Pleven
Accession: SCV004100884.1
First in ClinVar: Nov 11, 2023 Last updated: Nov 11, 2023 |
|
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Not provided
Affected status: yes
Allele origin:
unknown
|
GenomeConnect, ClinGen
Accession: SCV000607156.1
First in ClinVar: Oct 14, 2017 Last updated: Oct 14, 2017 |
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical … (more)
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Breast carcinoma (present)
Indication for testing: Diagnostic, Hereditary breast cancer
Age: 30-39 years
Sex: female
Testing laboratory: Color Genomics, Inc.
Date variant was reported to submitter: 2017-03-13
Testing laboratory interpretation: Pathogenic
|
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
GeneReviews
Accession: SCV000086949.3
First in ClinVar: Oct 01, 2013 Last updated: Oct 01, 2022 |
Comment:
Founder variant in Ashkenazi Jews; accounts for 26% of pathogenic variants in this population
|
|
| click to load more click to collapse | |||||
Citation text
Ladopolou-et-al.,-Cancer-Lett,-185:61,-2002
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1.
Comment:
This mutation is an insertion of one nucleotide (cytosine), resulting in a frameshift and the creation of a novel translational termination codon after 74 amino acid residues. The protein product thus produced is truncated and non-functional. This mutation has been described in the international bibliography (http://research.nhgri.nih.gov/projects/bic) and has been shown to be a founder mutation in a number of ethnic groups (PMID: 12142080). This mutation has been described in the mutation database ClinVar (Variation ID:17677).
Comment:
The c.5266dup;p.(Gln1756Profs*74) is a null frameshift variant (NMD) in the BRCA1 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevant exon to the transcript - PVS1_strong. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 17677; PMID: 15994883; PMID: 22430266) - PS4. The variant is present at low allele frequencies population databases (rs80357906 – gnomAD 0.001803%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic.
Comment:
ACMG criteria used to clasify this variant: PVS1, PM2, PS4
Comment:
ACMG classification criteria: PVS1 very strong, PS3 supporting, PS4 strong, PP1 strong
Comment:
PVS1, PS4_STR, BS1
Comment:
The BRCA1 c.5266dup; p.Gln1756ProfsTer74 variant, also known as 5382insC, has been described in individuals and families with hereditary breast and ovarian cancer, peritoneal cancer, and pancreatic cancer and is a known pathogenic founder variant (Bogdanova 2010, Elsakov 2010, Heidemann 2012, Simard 1994, Uglanitsa 2010, Zhang 2011). This variant is reported as pathogenic in ClinVar (Variation ID: 17677). It is found in the general population with an overall allele frequency of 0.02% (51/282892 alleles) in the Genome Aggregation Database. This variant causes a frameshift by duplicating a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. [**Use the AJ BRCA template under BRCA NGS, OR Make sure to add the AJ recommendations from that template "If this individual is of Ashkenazi Jewish ancestry…"**] References: Bogdanova NV et al. High frequency and allele-specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus. Clin Genet. 2010 78(4):364-72. PMID: 20569256. Elsakov P et al. The contribution of founder mutations in BRCA1 to breast and ovarian cancer in Lithuania. Clin Genet. 2010 78(4):373-6. PMID: 20345474. Heidemann S et al. Double heterozygosity for mutations in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management. Breast Cancer Res Treat. 2012 134(3):1229-39. PMID: 22535016. Simard J et al. Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families. Nat Genet. 1994 8(4):392-8. PMID: 7894492. Uglanitsa N et al. The contribution of founder mutations in BRCA1 to breast cancer in Belarus. Clin Genet. 2010 78(4):377-80. PMID: 20507347. Zhang S et al. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol Oncol. 2011 121(2):353-7. PMID: 21324516.
Comment:
The c.5266dup (p.Gln1756Profs*74) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 7894492, 26718727, 20569256, 21503673, 23232912, 26666763, 22430266, 19359128, 20730485, 22032251, 21324516, among others, referred as 5382C in some publications], pancreatic cancer [PMID 24737347, 26440929] and prostate cancer [PMID 27433846 ]. This variant is a founder mutation in the Ashkenazi Jewish population and is found with a high prevalence in Poland and Eastern Europe [PMID 20569256, 20345474, 20507347]. The estimated risk for carriers of this variant was 89% for breast cancer and 42% for ovarian cancer by age 70 [PMID 22430266]. This one bp duplication in exon 19 results in a frameshift and the creation of a premature stop codon. This variant is thus predicted to result in a loss of function of the protein. This variant has been detected in 19 individuals from the ExAC database (http://exac.broadinstitute.org/variant/17-41209079-T-TG). This variant thus classified as pathogenic.
Comment:
Frameshift variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5382insC or 5385insC; This variant is associated with the following publications: (PMID: 25859162, 25849179, 27160020, 26843898, 26852130, 26833046, 27025497, 27062684, 26681312, 29790872, 26440929, 30067863, 31336956, 32854451, 24372583, 21119707, 26656232, 26083025, 25476495, 24528374, 25195694, 22032251, 7894492, 16168118, 27223485, 26779294, 27433846, 26666763, 26718727, 29478780, 27425403, 22009639, 20569256, 21503673, 23232912, 20345474, 22430266, 29335925, 28285342, 22535016, 29339979, 23954390, 29433453, 29335924, 29492181, 21834074, 24737347, 19359128, 27914478, 28324225, 22666503, 27989354, 29907814, 20730485, 28091860, 28503720, 26556299, 10464624, 28423363, 20507347, 22006311, 25980754, 21324516, 29310832, 30333958, 30159786, 29161300, 30606148, 30152102, 28049106, 28111427, 30186769, 29961768, 30322717, 31090900, 31159747, 30113427, 23199084, 8841191, 30676620, 30489631, 31454914, 12771565, 31528241, 27741520, 29625052, 26689913, 32058061, 31447099, 32039725)
Comment:
This BRCA1 variant (rs80357906) is rare (<0.1%) in a large population dataset (gnomAD: 51/282892 total alleles, 0.018%, no homozygotes) and has been reported in ClinVar. This frameshift variant results in a premature stop codon in exon 19 of 23 likely leading to nonsense-mediated decay and lack of protein production. This variant, also known as 5382insC and 5385insC in the literature, is a common cause of breast and ovarian cancer in the Ashkenazi Jewish population and has been reported in individuals from other ethnicities. This variant has been associated with a 67% to 89% risk of breast cancer by age 70, and a 33% to 42% risk of ovarian cancer by age 70. This variant was also identified in the patient's mother (JHG1740-2). We consider c.5266dupC to be pathogenic.
Comment:
Variant summary: The BRCA1 c.5266dupC variant results in a frameshift, which alters the protein's amino acid sequence beginning at position 1756 and leads to a premature termination codon 73 amino acids downstream. It is predicted to cause a truncated or absent BRCA1 protein due to non-sense meditated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (such as c.5387C>A/p.Ser1796X, c.5417delC/Pro1806fsX28, etc). Mutation Taster predicts a damaging outcome for this variant, and functional studies have shown HR activity is significantly impaired by this variant (Bouwman_BRCA1_Cancer Discovery_2013). BRCA1 c.5266dupC was found in 19/121412 control chromosomes at a frequency of 0.0001565, which does not exceed maximal expected frequency of a pathogenic BRCA1 allele (0.0010005). The variant has been cited in hundreds of HBOC patients and is reported as a known common founder mutation in the literature. Additionally, this variant has been classified by multiple clinical labs and databases as pathogenic. Taken together, this variant was classified as disease variant/pathogenic.
Comment:
The c.5266dup (p.Gln1756ProfsTer74) variant identified in the BRCA1 gene is the duplication of a single nucleotide resulting in a frameshift at amino acid 1756/1863 (exon 19/23). This variant is predicted to incorporate a premature termination codon at approximately 74 amino acids downstream and result in either loss-of-function via nonsense mediated decay or protein truncation. This variant is found with low frequency in gnomAD(v3.1.2) (8 heterozygotes, 0 homozygotes; allele frequency: 1.972e-5), suggesting it is not a common benign variant in the populations represented in that database. The c.5266dup (p.Gln1756ProfsTer74) variant is reported in ClinVar as Pathogenic by an expert panel (VarID: 17677), and is one of the most frequently reported pathogenic variants in the BRCA1 gene. This variant has been reported in multiple affected individuals in the literature [PMID: 21119707, 24797986, 31706072, others]. Based on the available evidence c.5266dup(p.Gln1756ProfsTer74) variant is reported as Pathogenic.
Comment:
The BRCA1 c.5266dup (p.Gln1756ProfsTer74) variant, also referred to as c.5382insC or c.5382_5383insC, causes a shift in the translational reading frame that is predicted to result in premature termination of the protein. Loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay is expected. This variant has been previously identified in individuals with breast cancer, ovarian cancer, pancreatic cancer, and prostate cancer (PMID: 29335925; PMID: 29961768; PMID: 11802209; PMID: 29492181; PMID: 22430266). Further, this variant is one of three well-characterized founder variants in the Ashkenazi Jewish population, accounting for an estimated 26% of pathogenic variants detected in this population (GeneReviews PMID: 20301425). The highest frequency of this allele in the Genome Aggregation Database is 0.002314 in the Ashkenazi Jewish population (v2.1.1). This variant has been classified as pathogenic by >60 submitters in ClinVar, including a BRCA1 expert panel. Based on the available evidence, the c.5266dup (p.Gln1756ProfsTer74) variant is classified as pathogenic for hereditary breast and ovarian cancer.
Comment:
The BRCA1 c.5266dup (p.Gln1756Profs*74) variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. This variant has been reported in the published literature as a founder mutation in the Ashkenazi Jewish population and has been reported in multiple individuals and families affected with breast and/or ovarian cancer (PMIDs: 18694767 (2008), 19208665 (2009), 21119707 (2011), 30606148 (2019), 32438681 (2020), 35409996 (2022)), as well as prostate cancer (PMID: 36612302 (2023)). This variant has also been reported in affected and control individuals in a large-scale breast cancer association study (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/)). A functional study showed that this variant caused the complete loss of BRCA1 phosphopeptide binding activity (PMID: 15133502 (2004)). Based on the available information, this variant is classified as pathogenic.
Comment:
PP5, PS4_moderate, PVS1
Comment:
This variant has been identified by standard clinical testing. female patient with metastatic breast cancer Selected ACMG criteria: Pathogenic (I):PP5;PS4;PVS1
Comment:
This sequence change creates a premature translational stop signal (p.Gln1756Profs*74) in the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 108 amino acid(s) of the BRCA1 protein. This variant is present in population databases (rs397507247, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer. It is commonly reported in individuals of Ashkenazi Jewish ancestry (PMID: 9042909, 22185575, 22430266). This variant is also known as 5382insC and 5385insC. ClinVar contains an entry for this variant (Variation ID: 17677). This variant has been associated with a 67% to 89% risk of breast cancer by age 70, and a 33% to 42% risk of ovarian cancer by age 70 (PMID: 15994883, 22430266). This variant disrupts a region of the BRCA1 protein in which other variant(s) (Deletion (Exon 23)) have been determined to be pathogenic (PMID: 18431737, 24825132, 25428789; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Comment:
This variant (also known as 5382insC and 5385insC) inserts 1 nucleotide in exon 19 of the BRCA1 gene, causing a frameshift and a premature translational stop signal in the last exon. The mutant transcript is expected to escape nonsense-mediated decay and be expressed as a truncated protein that lacks the C-terminal BRCT domain. Experimental studies have shown that variant impacts BRCA1 function in homology-directed repair and subcellular localization assays (PMID: 14729053, 23867111). This variant is a well-known founder mutation in the Ashkenazi Jewish population and occurs at 0.13-0.28% minor allele frequency (PMID: 8841191, 9145676, 11466700, 30152102). This variant has been reported in numerous individuals affected with breast and/or ovarian cancer (PMID: 7545954, 7894492, 8531967, 9042909, 9150153, 17922257, 18334730, 21643751, 22430266, 25418591, 29335925, 30480775, 30606148, 30975216). This variant is the most globally frequent, pathogenic BRCA1 variant and has been reported in diverse populations in Africa, America, Asia and Europe (PMID: 24312913). The risk of female breast cancer among carriers of this mutation is 67-89% by age 70, and the risk of ovarian cancer is 22-42% by age 70 (PMID: 9145676, 15994883, 22430266). A breast cancer case-control meta-analysis has reported this variant in 97/60369 cases and 11/53450 controls with an estimated OR of 7.808 (95%CI 4.185 to 14.567) (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_000440). This variant has been identified in 51/282892 chromosomes (24/10370 Ashkenazi Jewish chromosomes and 25/129200 Non-Finnish European chromosomes) in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.
Comment:
ACMG Criteria: PM2_P; Variant was found in heterozygous state
Comment:
The p.Gln1756ProfsX74 variant in BRCA1 (also referred to as p.Gln1777fs) is a founder variant in the Ashkenazi Jewish population and has been reported in >1000 individuals with BRCA1-associated cancers (Abeliovich 1997 PMID: 9042909, Elwad 2011 PMID: 22185575, Breast Cancer Information Core (BIC) database). This variant has also been identified in 0.2% (24/103702) Ashkenazi Jewish and 0.02% (25/129200) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1756 and leads to a premature termination codon 74 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism in hereditary breast and ovarian cancer (HBOC). Furthermore, the p.Gln1756ProfsX74 variant was classified as Pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar ID 17677). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PS4, PVS1.
Comment:
The c.5266dupC (p.Q1756Pfs*74) alteration, located in exon 19 (coding exon 18) of the BRCA1 gene, consists of a duplication of C at position 5266, causing a translational frameshift with a predicted alternate stop codon after amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This alteration is one of three well-characterized Ashkenazi Jewish founder mutations, with an overall carrier frequency of nearly 0.5% in this population, but has also been shown to occur at high frequency in many other European populations (Hartge, 1999; Hamel, 2011; Kluz, 2018). Cumulative female breast cancer and ovarian cancer risks (by age 70) associated with this specific mutation have been estimated in the literature at 67% (range: 36-83%) and 33% (range: 8-50%), respectively (Antoniou, 2005). Of note, this mutation is also designated as 5382insC and 5385insC in the published literature. Based on the available evidence, this alteration is classified as pathogenic.
Comment:
The BRCA1 c.5266dup (p.Gln1756Profs*74) variant is one of the most common variants reported in Central and Eastern European families with high risk of breast and/or ovarian cancer (Janavicius R, PMID: 23199084). This variant causes a frameshift by inserting one nucleotide, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. This variant has been reported in the ClinVar database as a germline pathogenic variant by 10 submitters. Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as pathogenic.
Comment:
PVS1; PM5_PTC_Strong
Comment:
Criteria applied: PVS1,PS4,PM5_STR
Comment:
BRCA1: PVS1, PS4:Moderate
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Fanconi anaemia, complementation group S (MIM#617883), susceptibility to breast and ovarian cancer (MIM#604370) and susceptibility to pancreatic cancer (MIM#614320). (I) 0108 - This gene is associated with both recessive and dominant disease. Susceptibility to breast and ovarian cancer follows an autosomal dominant inheritance pattern, while Fanconi anaemia is inherited in an autosomal recessive pattern (OMIM). (I) 0112 - The condition associated with this gene has incomplete penetrance. The highest estimate for cancer risk in carriers of pathogenic variants is 80% by the age of 70 years (PMID: 30551077). (I) 0205 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with less than 1/3 of the protein sequence affected. (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 (v2 & v3: 53 heterozygotes, 0 homozygotes). (SP) 0701 - Other variants located downstream and predicted to result in a truncated protein comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0801 - This variant has very strong previous evidence of pathogenicity in unrelated individuals. It is regarded as pathogenic by multiple diagnostic laboratories including expert panel ENIGMA and associated with susceptibility to breast cancer (ClinVar). In addition, it is a founder mutation in Ashkenazi Jewish (GeneReviews). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Comment:
The BRCA1 c.5266dup (p.Gln1756ProfsTer74) change duplicates one nucleotide to cause a frameshift and the creation of a premature stop codon. This change is predicted to cause protein truncation. This variant, which is also known as c.5382insC in published literature, has been reported in several individuals with BRCA1-related cancers (PMID: 7894492, 9634504, 10739756, 22666503, 24737347, 26440929, 27433846, 32058061) and is an Ashkenazi Jewish founder mutation (PMID: 30152102). In summary, this variant meets criteria to be classified as pathogenic.
Comment:
The BRCA1 c.5266dupC variant is predicted to result in a frameshift and premature protein termination (p.Gln1756Profs*74). This variant (also described as 5382insC, 5385insC, or 5329dupC) has been reported in multiple individuals with autosomal dominant hereditary breast and ovarian cancer syndrome (HBOC) (OMIM #604370; Bogdanova et al. 2010. PubMed ID: 20569256; Alemar et al. 2016. PubMed ID: 27425403; Azzollini et al. 2016. PubMed ID: 27062684; Hamel et al. 2011. PubMed ID: 21119707). It is a founder variant in the Ashkenazi Jewish population and is reported in 0.23% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. It is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/17677/). Frameshift variants in BRCA1 are expected to be pathogenic. In summary, this variant is interpreted as pathogenic.
Comment:
DNA sequence analysis of the BRCA1 gene demonstrated a single base pair duplication in exon 19, c.5266dup. This pathogenic sequence change results in an amino acid frameshift and creates a premature stop codon 74 amino acids downstream of the change, p.Gln1756Profs*74. This pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated BRCA1 protein with potentially abnormal function. This sequence change has been described in the gnomAD database with a frequency of 0.23% in the Ashkenazi Jewish subpopulation (dbSNP rs1217805587). This pathogenic sequence change is a well-described pathogenic BRCA1 variant and a known founder mutation in the Ashkenazi Jewish population reported in multiple individuals with hereditary breast and ovarian cancer syndrome (PMID: 12473589, 15131399, 9042909, 22430266, 24764757, 26976419). The c.5266dup sequence change is also referred to as 5382insC in the scientific literature
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Comment:
Founder variant in Ashkenazi Jews; accounts for 26% of pathogenic variants in this population
Germline Functional Evidence
| Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|---|---|---|---|---|
|
has functional consequence
|
Bioinformatics dept., Datar Cancer Genetics Limited, India
Accession: SCV000584019.1
|
|
Citation text
Ladopolou-et-al.,-Cancer-Lett,-185:61,-2002
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1.
Comment:
This mutation is an insertion of one nucleotide (cytosine), resulting in a frameshift and the creation of a novel translational termination codon after 74 amino acid residues. The protein product thus produced is truncated and non-functional. This mutation has been described in the international bibliography (http://research.nhgri.nih.gov/projects/bic) and has been shown to be a founder mutation in a number of ethnic groups (PMID: 12142080). This mutation has been described in the mutation database ClinVar (Variation ID:17677).
Comment:
The c.5266dup;p.(Gln1756Profs*74) is a null frameshift variant (NMD) in the BRCA1 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevant exon to the transcript - PVS1_strong. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 17677; PMID: 15994883; PMID: 22430266) - PS4. The variant is present at low allele frequencies population databases (rs80357906 – gnomAD 0.001803%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic.
Comment:
ACMG criteria used to clasify this variant: PVS1, PM2, PS4
Comment:
ACMG classification criteria: PVS1 very strong, PS3 supporting, PS4 strong, PP1 strong
Comment:
PVS1, PS4_STR, BS1
Comment:
The BRCA1 c.5266dup; p.Gln1756ProfsTer74 variant, also known as 5382insC, has been described in individuals and families with hereditary breast and ovarian cancer, peritoneal cancer, and pancreatic cancer and is a known pathogenic founder variant (Bogdanova 2010, Elsakov 2010, Heidemann 2012, Simard 1994, Uglanitsa 2010, Zhang 2011). This variant is reported as pathogenic in ClinVar (Variation ID: 17677). It is found in the general population with an overall allele frequency of 0.02% (51/282892 alleles) in the Genome Aggregation Database. This variant causes a frameshift by duplicating a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. [**Use the AJ BRCA template under BRCA NGS, OR Make sure to add the AJ recommendations from that template "If this individual is of Ashkenazi Jewish ancestry…"**] References: Bogdanova NV et al. High frequency and allele-specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus. Clin Genet. 2010 78(4):364-72. PMID: 20569256. Elsakov P et al. The contribution of founder mutations in BRCA1 to breast and ovarian cancer in Lithuania. Clin Genet. 2010 78(4):373-6. PMID: 20345474. Heidemann S et al. Double heterozygosity for mutations in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management. Breast Cancer Res Treat. 2012 134(3):1229-39. PMID: 22535016. Simard J et al. Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families. Nat Genet. 1994 8(4):392-8. PMID: 7894492. Uglanitsa N et al. The contribution of founder mutations in BRCA1 to breast cancer in Belarus. Clin Genet. 2010 78(4):377-80. PMID: 20507347. Zhang S et al. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol Oncol. 2011 121(2):353-7. PMID: 21324516.
Comment:
The c.5266dup (p.Gln1756Profs*74) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 7894492, 26718727, 20569256, 21503673, 23232912, 26666763, 22430266, 19359128, 20730485, 22032251, 21324516, among others, referred as 5382C in some publications], pancreatic cancer [PMID 24737347, 26440929] and prostate cancer [PMID 27433846 ]. This variant is a founder mutation in the Ashkenazi Jewish population and is found with a high prevalence in Poland and Eastern Europe [PMID 20569256, 20345474, 20507347]. The estimated risk for carriers of this variant was 89% for breast cancer and 42% for ovarian cancer by age 70 [PMID 22430266]. This one bp duplication in exon 19 results in a frameshift and the creation of a premature stop codon. This variant is thus predicted to result in a loss of function of the protein. This variant has been detected in 19 individuals from the ExAC database (http://exac.broadinstitute.org/variant/17-41209079-T-TG). This variant thus classified as pathogenic.
Comment:
Frameshift variant predicted to result in protein truncation in a gene for which loss-of-function is a known mechanism of disease; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5382insC or 5385insC; This variant is associated with the following publications: (PMID: 25859162, 25849179, 27160020, 26843898, 26852130, 26833046, 27025497, 27062684, 26681312, 29790872, 26440929, 30067863, 31336956, 32854451, 24372583, 21119707, 26656232, 26083025, 25476495, 24528374, 25195694, 22032251, 7894492, 16168118, 27223485, 26779294, 27433846, 26666763, 26718727, 29478780, 27425403, 22009639, 20569256, 21503673, 23232912, 20345474, 22430266, 29335925, 28285342, 22535016, 29339979, 23954390, 29433453, 29335924, 29492181, 21834074, 24737347, 19359128, 27914478, 28324225, 22666503, 27989354, 29907814, 20730485, 28091860, 28503720, 26556299, 10464624, 28423363, 20507347, 22006311, 25980754, 21324516, 29310832, 30333958, 30159786, 29161300, 30606148, 30152102, 28049106, 28111427, 30186769, 29961768, 30322717, 31090900, 31159747, 30113427, 23199084, 8841191, 30676620, 30489631, 31454914, 12771565, 31528241, 27741520, 29625052, 26689913, 32058061, 31447099, 32039725)
Comment:
This BRCA1 variant (rs80357906) is rare (<0.1%) in a large population dataset (gnomAD: 51/282892 total alleles, 0.018%, no homozygotes) and has been reported in ClinVar. This frameshift variant results in a premature stop codon in exon 19 of 23 likely leading to nonsense-mediated decay and lack of protein production. This variant, also known as 5382insC and 5385insC in the literature, is a common cause of breast and ovarian cancer in the Ashkenazi Jewish population and has been reported in individuals from other ethnicities. This variant has been associated with a 67% to 89% risk of breast cancer by age 70, and a 33% to 42% risk of ovarian cancer by age 70. This variant was also identified in the patient's mother (JHG1740-2). We consider c.5266dupC to be pathogenic.
Comment:
Variant summary: The BRCA1 c.5266dupC variant results in a frameshift, which alters the protein's amino acid sequence beginning at position 1756 and leads to a premature termination codon 73 amino acids downstream. It is predicted to cause a truncated or absent BRCA1 protein due to non-sense meditated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (such as c.5387C>A/p.Ser1796X, c.5417delC/Pro1806fsX28, etc). Mutation Taster predicts a damaging outcome for this variant, and functional studies have shown HR activity is significantly impaired by this variant (Bouwman_BRCA1_Cancer Discovery_2013). BRCA1 c.5266dupC was found in 19/121412 control chromosomes at a frequency of 0.0001565, which does not exceed maximal expected frequency of a pathogenic BRCA1 allele (0.0010005). The variant has been cited in hundreds of HBOC patients and is reported as a known common founder mutation in the literature. Additionally, this variant has been classified by multiple clinical labs and databases as pathogenic. Taken together, this variant was classified as disease variant/pathogenic.
Comment:
The c.5266dup (p.Gln1756ProfsTer74) variant identified in the BRCA1 gene is the duplication of a single nucleotide resulting in a frameshift at amino acid 1756/1863 (exon 19/23). This variant is predicted to incorporate a premature termination codon at approximately 74 amino acids downstream and result in either loss-of-function via nonsense mediated decay or protein truncation. This variant is found with low frequency in gnomAD(v3.1.2) (8 heterozygotes, 0 homozygotes; allele frequency: 1.972e-5), suggesting it is not a common benign variant in the populations represented in that database. The c.5266dup (p.Gln1756ProfsTer74) variant is reported in ClinVar as Pathogenic by an expert panel (VarID: 17677), and is one of the most frequently reported pathogenic variants in the BRCA1 gene. This variant has been reported in multiple affected individuals in the literature [PMID: 21119707, 24797986, 31706072, others]. Based on the available evidence c.5266dup(p.Gln1756ProfsTer74) variant is reported as Pathogenic.
Comment:
The BRCA1 c.5266dup (p.Gln1756ProfsTer74) variant, also referred to as c.5382insC or c.5382_5383insC, causes a shift in the translational reading frame that is predicted to result in premature termination of the protein. Loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay is expected. This variant has been previously identified in individuals with breast cancer, ovarian cancer, pancreatic cancer, and prostate cancer (PMID: 29335925; PMID: 29961768; PMID: 11802209; PMID: 29492181; PMID: 22430266). Further, this variant is one of three well-characterized founder variants in the Ashkenazi Jewish population, accounting for an estimated 26% of pathogenic variants detected in this population (GeneReviews PMID: 20301425). The highest frequency of this allele in the Genome Aggregation Database is 0.002314 in the Ashkenazi Jewish population (v2.1.1). This variant has been classified as pathogenic by >60 submitters in ClinVar, including a BRCA1 expert panel. Based on the available evidence, the c.5266dup (p.Gln1756ProfsTer74) variant is classified as pathogenic for hereditary breast and ovarian cancer.
Comment:
The BRCA1 c.5266dup (p.Gln1756Profs*74) variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. This variant has been reported in the published literature as a founder mutation in the Ashkenazi Jewish population and has been reported in multiple individuals and families affected with breast and/or ovarian cancer (PMIDs: 18694767 (2008), 19208665 (2009), 21119707 (2011), 30606148 (2019), 32438681 (2020), 35409996 (2022)), as well as prostate cancer (PMID: 36612302 (2023)). This variant has also been reported in affected and control individuals in a large-scale breast cancer association study (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/)). A functional study showed that this variant caused the complete loss of BRCA1 phosphopeptide binding activity (PMID: 15133502 (2004)). Based on the available information, this variant is classified as pathogenic.
Comment:
PP5, PS4_moderate, PVS1
Comment:
This variant has been identified by standard clinical testing. female patient with metastatic breast cancer Selected ACMG criteria: Pathogenic (I):PP5;PS4;PVS1
Comment:
This sequence change creates a premature translational stop signal (p.Gln1756Profs*74) in the BRCA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 108 amino acid(s) of the BRCA1 protein. This variant is present in population databases (rs397507247, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer. It is commonly reported in individuals of Ashkenazi Jewish ancestry (PMID: 9042909, 22185575, 22430266). This variant is also known as 5382insC and 5385insC. ClinVar contains an entry for this variant (Variation ID: 17677). This variant has been associated with a 67% to 89% risk of breast cancer by age 70, and a 33% to 42% risk of ovarian cancer by age 70 (PMID: 15994883, 22430266). This variant disrupts a region of the BRCA1 protein in which other variant(s) (Deletion (Exon 23)) have been determined to be pathogenic (PMID: 18431737, 24825132, 25428789; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Comment:
This variant (also known as 5382insC and 5385insC) inserts 1 nucleotide in exon 19 of the BRCA1 gene, causing a frameshift and a premature translational stop signal in the last exon. The mutant transcript is expected to escape nonsense-mediated decay and be expressed as a truncated protein that lacks the C-terminal BRCT domain. Experimental studies have shown that variant impacts BRCA1 function in homology-directed repair and subcellular localization assays (PMID: 14729053, 23867111). This variant is a well-known founder mutation in the Ashkenazi Jewish population and occurs at 0.13-0.28% minor allele frequency (PMID: 8841191, 9145676, 11466700, 30152102). This variant has been reported in numerous individuals affected with breast and/or ovarian cancer (PMID: 7545954, 7894492, 8531967, 9042909, 9150153, 17922257, 18334730, 21643751, 22430266, 25418591, 29335925, 30480775, 30606148, 30975216). This variant is the most globally frequent, pathogenic BRCA1 variant and has been reported in diverse populations in Africa, America, Asia and Europe (PMID: 24312913). The risk of female breast cancer among carriers of this mutation is 67-89% by age 70, and the risk of ovarian cancer is 22-42% by age 70 (PMID: 9145676, 15994883, 22430266). A breast cancer case-control meta-analysis has reported this variant in 97/60369 cases and 11/53450 controls with an estimated OR of 7.808 (95%CI 4.185 to 14.567) (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_000440). This variant has been identified in 51/282892 chromosomes (24/10370 Ashkenazi Jewish chromosomes and 25/129200 Non-Finnish European chromosomes) in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease. Based on the available evidence, this variant is classified as Pathogenic.
Comment:
ACMG Criteria: PM2_P; Variant was found in heterozygous state
Comment:
The p.Gln1756ProfsX74 variant in BRCA1 (also referred to as p.Gln1777fs) is a founder variant in the Ashkenazi Jewish population and has been reported in >1000 individuals with BRCA1-associated cancers (Abeliovich 1997 PMID: 9042909, Elwad 2011 PMID: 22185575, Breast Cancer Information Core (BIC) database). This variant has also been identified in 0.2% (24/103702) Ashkenazi Jewish and 0.02% (25/129200) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1756 and leads to a premature termination codon 74 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism in hereditary breast and ovarian cancer (HBOC). Furthermore, the p.Gln1756ProfsX74 variant was classified as Pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar ID 17677). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PS4, PVS1.
Comment:
The c.5266dupC (p.Q1756Pfs*74) alteration, located in exon 19 (coding exon 18) of the BRCA1 gene, consists of a duplication of C at position 5266, causing a translational frameshift with a predicted alternate stop codon after amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This alteration is one of three well-characterized Ashkenazi Jewish founder mutations, with an overall carrier frequency of nearly 0.5% in this population, but has also been shown to occur at high frequency in many other European populations (Hartge, 1999; Hamel, 2011; Kluz, 2018). Cumulative female breast cancer and ovarian cancer risks (by age 70) associated with this specific mutation have been estimated in the literature at 67% (range: 36-83%) and 33% (range: 8-50%), respectively (Antoniou, 2005). Of note, this mutation is also designated as 5382insC and 5385insC in the published literature. Based on the available evidence, this alteration is classified as pathogenic.
Comment:
The BRCA1 c.5266dup (p.Gln1756Profs*74) variant is one of the most common variants reported in Central and Eastern European families with high risk of breast and/or ovarian cancer (Janavicius R, PMID: 23199084). This variant causes a frameshift by inserting one nucleotide, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. This variant has been reported in the ClinVar database as a germline pathogenic variant by 10 submitters. Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as pathogenic.
Comment:
PVS1; PM5_PTC_Strong
Comment:
Criteria applied: PVS1,PS4,PM5_STR
Comment:
BRCA1: PVS1, PS4:Moderate
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Fanconi anaemia, complementation group S (MIM#617883), susceptibility to breast and ovarian cancer (MIM#604370) and susceptibility to pancreatic cancer (MIM#614320). (I) 0108 - This gene is associated with both recessive and dominant disease. Susceptibility to breast and ovarian cancer follows an autosomal dominant inheritance pattern, while Fanconi anaemia is inherited in an autosomal recessive pattern (OMIM). (I) 0112 - The condition associated with this gene has incomplete penetrance. The highest estimate for cancer risk in carriers of pathogenic variants is 80% by the age of 70 years (PMID: 30551077). (I) 0205 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with less than 1/3 of the protein sequence affected. (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 (v2 & v3: 53 heterozygotes, 0 homozygotes). (SP) 0701 - Other variants located downstream and predicted to result in a truncated protein comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0801 - This variant has very strong previous evidence of pathogenicity in unrelated individuals. It is regarded as pathogenic by multiple diagnostic laboratories including expert panel ENIGMA and associated with susceptibility to breast cancer (ClinVar). In addition, it is a founder mutation in Ashkenazi Jewish (GeneReviews). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Comment:
The BRCA1 c.5266dup (p.Gln1756ProfsTer74) change duplicates one nucleotide to cause a frameshift and the creation of a premature stop codon. This change is predicted to cause protein truncation. This variant, which is also known as c.5382insC in published literature, has been reported in several individuals with BRCA1-related cancers (PMID: 7894492, 9634504, 10739756, 22666503, 24737347, 26440929, 27433846, 32058061) and is an Ashkenazi Jewish founder mutation (PMID: 30152102). In summary, this variant meets criteria to be classified as pathogenic.
Comment:
The BRCA1 c.5266dupC variant is predicted to result in a frameshift and premature protein termination (p.Gln1756Profs*74). This variant (also described as 5382insC, 5385insC, or 5329dupC) has been reported in multiple individuals with autosomal dominant hereditary breast and ovarian cancer syndrome (HBOC) (OMIM #604370; Bogdanova et al. 2010. PubMed ID: 20569256; Alemar et al. 2016. PubMed ID: 27425403; Azzollini et al. 2016. PubMed ID: 27062684; Hamel et al. 2011. PubMed ID: 21119707). It is a founder variant in the Ashkenazi Jewish population and is reported in 0.23% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. It is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/17677/). Frameshift variants in BRCA1 are expected to be pathogenic. In summary, this variant is interpreted as pathogenic.
Comment:
DNA sequence analysis of the BRCA1 gene demonstrated a single base pair duplication in exon 19, c.5266dup. This pathogenic sequence change results in an amino acid frameshift and creates a premature stop codon 74 amino acids downstream of the change, p.Gln1756Profs*74. This pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated BRCA1 protein with potentially abnormal function. This sequence change has been described in the gnomAD database with a frequency of 0.23% in the Ashkenazi Jewish subpopulation (dbSNP rs1217805587). This pathogenic sequence change is a well-described pathogenic BRCA1 variant and a known founder mutation in the Ashkenazi Jewish population reported in multiple individuals with hereditary breast and ovarian cancer syndrome (PMID: 12473589, 15131399, 9042909, 22430266, 24764757, 26976419). The c.5266dup sequence change is also referred to as 5382insC in the scientific literature
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Comment:
Founder variant in Ashkenazi Jews; accounts for 26% of pathogenic variants in this population
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Prevalence of Germline BRCA1/2 Variants in Ashkenazi and Non-Ashkenazi Prostate Cancer Populations: A Systematic Review and Meta-Analysis. | Cioffi A | Cancers | 2023 | PMID: 36612302 |
| BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer. | Adam MP | - | 2023 | PMID: 20301425 |
| Double heterozygous pathogenic variants prevalence in a cohort of patients with hereditary breast cancer. | Megid TBC | Frontiers in oncology | 2022 | PMID: 36003761 |
| Prevalence of Clinically Relevant Germline BRCA Variants in a Large Unselected South African Breast and Ovarian Cancer Cohort: A Public Sector Experience. | Van der Merwe NC | Frontiers in genetics | 2022 | DOI: 10.3389/fgene.2022.834265 |
| Spectrum of BRCA1/2 Mutations in Romanian Breast and Ovarian Cancer Patients. | Vidra R | International journal of environmental research and public health | 2022 | PMID: 35409996 |
| Prevalence of mutations in BRCA and MMR genes in patients affected with hereditary endometrial cancer. | Vietri MT | Medical oncology (Northwood, London, England) | 2021 | PMID: 33484353 |
| Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
| Double heterozygosity for TP53 and BRCA1 mutations: clinical implications in populations with founder mutations. | Shani H | Breast cancer research and treatment | 2021 | PMID: 33449224 |
| Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario. | Lerner-Ellis J | Journal of cancer research and clinical oncology | 2021 | PMID: 32885271 |
| Detection of Germline Mutations in a Cohort of 139 Patients with Bilateral Breast Cancer by Multi-Gene Panel Testing: Impact of Pathogenic Variants in Other Genes beyond BRCA1/2. | Fanale D | Cancers | 2020 | PMID: 32854451 |
| Population genetic screening efficiently identifies carriers of autosomal dominant diseases. | Grzymski JJ | Nature medicine | 2020 | PMID: 32719484 |
| Spectrum of Germline BRCA1 and BRCA2 Variants Identified in 2351 Ovarian and Breast Cancer Patients Referring to a Reference Cancer Hospital of Rome. | Santonocito C | Cancers | 2020 | PMID: 32438681 |
| Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes. | De Talhouet S | Scientific reports | 2020 | PMID: 32341426 |
| Rare germline genetic variants and risk of aggressive prostate cancer. | Nguyen-Dumont T | International journal of cancer | 2020 | PMID: 32338768 |
| BRCA and PALB2 mutations in a cohort of male breast cancer with one bilateral case. | Vietri MT | European journal of medical genetics | 2020 | PMID: 32058061 |
| Germline variants in DNA repair genes associated with hereditary breast and ovarian cancer syndrome: analysis of a 21 gene panel in the Brazilian population. | da Costa E Silva Carvalho S | BMC medical genomics | 2020 | PMID: 32039725 |
| Next-Generation Sequencing Identifies BRCA1 and/or BRCA2 Mutations in Women at High Hereditary Risk for Breast Cancer with Shorter Telomere Length. | Peker Eyüboğlu İ | Omics : a journal of integrative biology | 2020 | PMID: 31851867 |
| Spectrum and prevalence of BRCA1/2 germline mutations in Pakistani breast cancer patients: results from a large comprehensive study. | Rashid MU | Hereditary cancer in clinical practice | 2019 | PMID: 31528241 |
| A Multi-Center Study of BRCA1 and BRCA2 Germline Mutations in Mexican-Mestizo Breast Cancer Families Reveals Mutations Unreported in Latin American Population. | Millan Catalan O | Cancers | 2019 | PMID: 31454914 |
| Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network. | eMERGE Consortium. Electronic address: [email protected] | American journal of human genetics | 2019 | PMID: 31447099 |
| Insights into BRCA Cancer Predisposition from Integrated Germline and Somatic Analyses in 7632 Cancers. | Yost S | JNCI cancer spectrum | 2019 | PMID: 31360904 |
| Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations. | Tsaousis GN | BMC cancer | 2019 | PMID: 31159747 |
| Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers. | Nones K | Annals of oncology : official journal of the European Society for Medical Oncology | 2019 | PMID: 31090900 |
| Next-generation sequencing of BRCA1 and BRCA2 genes for rapid detection of germline mutations in hereditary breast/ovarian cancer. | Nicolussi A | PeerJ | 2019 | PMID: 31065452 |
| Contribution of BRCA1 5382insC mutation in triple negative breast cancer in Tunisia. | Mahfoudh W | Journal of translational medicine | 2019 | PMID: 30975216 |
| Association of Inherited Pathogenic Variants in Checkpoint Kinase 2 (CHEK2) With Susceptibility to Testicular Germ Cell Tumors. | AlDubayan SH | JAMA oncology | 2019 | PMID: 30676620 |
| Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy. | Rizzolo P | International journal of cancer | 2019 | PMID: 30613976 |
| Prevalence of BRCA1 and BRCA2 pathogenic and likely pathogenic variants in non-selected ovarian carcinoma patients in Brazil. | Cotrim DP | BMC cancer | 2019 | PMID: 30606148 |
| Common genetic variants contribute to incomplete penetrance: evidence from cancer-free BRCA1 mutation carriers. | Downs B | European journal of cancer (Oxford, England : 1990) | 2019 | PMID: 30551077 |
| Uterine cancer in Jewish Israeli BRCA1/2 mutation carriers. | Laitman Y | Cancer | 2019 | PMID: 30489631 |
| Prevalence of nonfounder BRCA1/2 mutations in Ashkenazi Jewish patients presenting for genetic testing at a hereditary breast and ovarian cancer center. | Frey MK | Cancer | 2019 | PMID: 30480775 |
| Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer. | Yurgelun MB | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 29961768 |
| The Ethnic-Specific Spectrum of Germline Nucleotide Variants in DNA Damage Response and Repair Genes in Hereditary Breast and Ovarian Cancer Patients of Tatar Descent. | Brovkina OI | Frontiers in oncology | 2018 | PMID: 30333958 |
| Germline pathogenic variants identified in women with ovarian tumors. | Carter NJ | Gynecologic oncology | 2018 | PMID: 30322717 |
| BRCA1 and BRCA2 Mutations Other Than the Founder Alleles Among Ashkenazi Jewish in the Population of Argentina. | Solano AR | Frontiers in oncology | 2018 | PMID: 30186769 |
| A portrait of germline mutation in Brazilian at-risk for hereditary breast cancer. | de Souza Timoteo AR | Breast cancer research and treatment | 2018 | PMID: 30159786 |
| Hereditary cancer screening: Case reports and review of literature on ten Ashkenazi Jewish founder mutations. | Cox DM | Molecular genetics & genomic medicine | 2018 | PMID: 30152102 |
| Germline Variants and Risk for Pancreatic Cancer: A Systematic Review and Emerging Concepts. | Zhan W | Pancreas | 2018 | PMID: 30113427 |
| Prospective study of germline genetic testing in incident cases of pancreatic adenocarcinoma. | Brand R | Cancer | 2018 | PMID: 30067863 |
| The germline mutational landscape of BRCA1 and BRCA2 in Brazil. | Palmero EI | Scientific reports | 2018 | PMID: 29907814 |
| Genomic sequencing identifies secondary findings in a cohort of parent study participants. | Thompson ML | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 29790872 |
| Pathogenic Germline Variants in 10,389 Adult Cancers. | Huang KL | Cell | 2018 | PMID: 29625052 |
| Frequency of BRCA1 and BRCA2 causative founder variants in ovarian cancer patients in South-East Poland. | Kluz T | Hereditary cancer in clinical practice | 2018 | PMID: 29492181 |
| Inherited DNA-Repair Defects in Colorectal Cancer. | AlDubayan SH | American journal of human genetics | 2018 | PMID: 29478780 |
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| Male BRCA mutation carriers: clinical characteristics and cancer spectrum. | Ibrahim M | BMC cancer | 2018 | PMID: 29433453 |
| BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway. | Heramb C | Hereditary cancer in clinical practice | 2018 | PMID: 29339979 |
| Germline deleterious mutations in genes other than BRCA2 are infrequent in male breast cancer. | Fostira F | Breast cancer research and treatment | 2018 | PMID: 29335925 |
| BRCA1 and BRCA2 germline variants in breast cancer patients from the Republic of Macedonia. | Jakimovska M | Breast cancer research and treatment | 2018 | PMID: 29335924 |
| Comprehensive BRCA mutation analysis in the Greek population. Experience from a single clinical diagnostic center. | Apessos A | Cancer genetics | 2018 | PMID: 29310832 |
| BRCA1 and BRCA2 mutational profile and prevalence in hereditary breast and ovarian cancer (HBOC) probands from Southern Brazil: Are international testing criteria appropriate for this specific population? | Alemar B | PloS one | 2017 | PMID: 29161300 |
| Contribution of germline mutations in cancer predisposition genes to tumor etiology in young women diagnosed with invasive breast cancer. | Rummel SK | Breast cancer research and treatment | 2017 | PMID: 28503720 |
| Multiple-gene panel analysis in a case series of 255 women with hereditary breast and ovarian cancer. | Tedaldi G | Oncotarget | 2017 | PMID: 28423363 |
| Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study. | Meisel C | Archives of gynecology and obstetrics | 2017 | PMID: 28324225 |
| Prevalence of two BRCA1 mutations, 5382insC and 300T > G, in ovarian cancer patients from Ukraine. | Gorodetska I | Familial cancer | 2017 | PMID: 28285342 |
| Identification of a Novel BRCA1 Pathogenic Mutation in Korean Patients Following Reclassification of BRCA1 and BRCA2 Variants According to the ACMG Standards and Guidelines Using Relevant Ethnic Controls. | Park JS | Cancer research and treatment | 2017 | PMID: 28111427 |
| Retesting BRCA1/BRCA2 mutation negative male breast cancer patients using next generation sequencing technologies. | Rizzolo P | Breast cancer research and treatment | 2017 | PMID: 28091860 |
| Linking uterine serous carcinoma to BRCA1/2-associated cancer syndrome: A meta-analysis and case report. | de Jonge MM | European journal of cancer (Oxford, England : 1990) | 2017 | PMID: 28049106 |
| Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death. | Na R | European urology | 2017 | PMID: 27989354 |
| Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil. | Maistro S | BMC cancer | 2016 | PMID: 27914478 |
| Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry. | Fernandes GC | Oncotarget | 2016 | PMID: 27741520 |
| Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. | Pritchard CC | The New England journal of medicine | 2016 | PMID: 27433846 |
| Prevalence of Hispanic BRCA1 and BRCA2 mutations among hereditary breast and ovarian cancer patients from Brazil reveals differences among Latin American populations. | Alemar B | Cancer genetics | 2016 | PMID: 27425403 |
| Mutation detection rates associated with specific selection criteria for BRCA1/2 testing in 1854 high-risk families: A monocentric Italian study. | Azzollini J | European journal of internal medicine | 2016 | PMID: 27062684 |
| Genetic characterization of early onset ovarian carcinoma. | Bernards SS | Gynecologic oncology | 2016 | PMID: 26718727 |
| Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. | Susswein LR | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26681312 |
| Screening of the BRCA1 gene in Brazilian patients with breast and/or ovarian cancer via high-resolution melting reaction analysis. | de Oliveira ES | Familial cancer | 2016 | PMID: 26666763 |
| Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA. | Schrader KA | JAMA oncology | 2016 | PMID: 26556299 |
| Patterns and functional implications of rare germline variants across 12 cancer types. | Lu C | Nature communications | 2015 | PMID: 26689913 |
| Identification of germline genetic mutations in patients with pancreatic cancer. | Salo-Mullen EE | Cancer | 2015 | PMID: 26440929 |
| Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome. | Yurgelun MB | Gastroenterology | 2015 | PMID: 25980754 |
| Inherited predisposition to breast cancer among African American women. | Churpek JE | Breast cancer research and treatment | 2015 | PMID: 25428789 |
| Screening for common mutations in BRCA1 and BRCA2 genes: interest in genetic testing of Tunisian families with breast and/or ovarian cancer. | Fourati A | Bulletin du cancer | 2014 | PMID: 25418591 |
| Assessment of individuals with BRCA1 and BRCA2 large rearrangements in high-risk breast and ovarian cancer families. | Arnold AG | Breast cancer research and treatment | 2014 | PMID: 24825132 |
| BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high-risk pancreatic cancer screening and pancreatic cancer cohorts. | Lucas AL | Cancer | 2014 | PMID: 24737347 |
| Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. | Cunningham JM | Scientific reports | 2014 | PMID: 24504028 |
| Analysis of induced pluripotent stem cells from a BRCA1 mutant family. | Soyombo AA | Stem cell reports | 2013 | PMID: 24319668 |
| A comprehensive focus on global spectrum of BRCA1 and BRCA2 mutations in breast cancer. | Karami F | BioMed research international | 2013 | PMID: 24312913 |
| Co-occurrence of multiple sclerosis and cancer in a BRCA1 positive family. | Holzmann C | European journal of medical genetics | 2013 | PMID: 23954390 |
| A high-throughput functional complementation assay for classification of BRCA1 missense variants. | Bouwman P | Cancer discovery | 2013 | PMID: 23867111 |
| Frequency of 5382insC mutation of BRCA1 gene among breast cancer patients: an experience from Eastern India. | Chakraborty A | Familial cancer | 2013 | PMID: 23232912 |
| BRCA2 mutations and triple-negative breast cancer. | Meyer P | PloS one | 2012 | PMID: 22666503 |
| Double heterozygosity for mutations in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management. | Heidemann S | Breast cancer research and treatment | 2012 | PMID: 22535016 |
| Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers. | Finkelman BS | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2012 | PMID: 22430266 |
| Predictive factors for BRCA1/BRCA2 mutations in women with ductal carcinoma in situ. | Bayraktar S | Cancer | 2012 | PMID: 22009639 |
| The risk of breast cancer in women with a BRCA1 mutation from North America and Poland. | Lubinski J | International journal of cancer | 2012 | PMID: 21834074 |
| Common BRCA1 and BRCA2 mutations in breast cancer families: a meta-analysis from systematic review. | Wang F | Molecular biology reports | 2012 | PMID: 21643751 |
| Prevalence of the BRCA1 founder mutation c.5266dupin Brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome. | Ewald IP | Hereditary cancer in clinical practice | 2011 | PMID: 22185575 |
| Genotype-phenotype correlations among BRCA1 4153delA and 5382insC mutation carriers from Latvia. | Plakhins G | BMC medical genetics | 2011 | PMID: 22032251 |
| Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. | Walsh T | Proceedings of the National Academy of Sciences of the United States of America | 2011 | PMID: 22006311 |
| Prevalence of the most frequent BRCA1 mutations in Polish population. | Brozek I | Journal of applied genetics | 2011 | PMID: 21503673 |
| Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. | Zhang S | Gynecologic oncology | 2011 | PMID: 21324516 |
| On the origin and diffusion of BRCA1 c.5266dupC (5382insC) in European populations. | Hamel N | European journal of human genetics : EJHG | 2011 | PMID: 21119707 |
| Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control. | Janavičius R | The EPMA journal | 2010 | PMID: 23199084 |
| Maternal and paternal lineage double heterozygosity alteration in familial breast cancer: a first case report. | Pilato B | Breast cancer research and treatment | 2010 | PMID: 20730485 |
| High frequency and allele-specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus. | Bogdanova NV | Clinical genetics | 2010 | PMID: 20569256 |
| The contribution of founder mutations in BRCA1 to breast cancer in Belarus. | Uglanitsa N | Clinical genetics | 2010 | PMID: 20507347 |
| The contribution of founder mutations in BRCA1 to breast and ovarian cancer in Lithuania. | Elsakov P | Clinical genetics | 2010 | PMID: 20345474 |
| First case of invasive breast cancer following prophylactic bilateral skin sparing mastectomy in a BRCA1 mutation carrier. | Maarse W | European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology | 2009 | PMID: 19359128 |
| Genetic services have value beyond BRCA1/2 testing. | Hall MJ | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2009 | PMID: 19208665 |
| Ovarian cancer patient with germline mutations in both BRCA1 and NBN genes. | Porhanova NV | Cancer genetics and cytogenetics | 2008 | PMID: 18940477 |
| Germline BRCA1 mutations predispose to pancreatic adenocarcinoma. | Al-Sukhni W | Human genetics | 2008 | PMID: 18762988 |
| Molecular and in silico analysis of BRCA1 and BRCA2 variants. | Tommasi S | Mutation research | 2008 | PMID: 18694767 |
| MLPA screening in the BRCA1 gene from 1,506 German hereditary breast cancer cases: novel deletions, frequent involvement of exon 17, and occurrence in single early-onset cases. | Engert S | Human mutation | 2008 | PMID: 18431737 |
| Complete mutation screening and haplotype characterization of BRCA1 gene in Tunisian patients with familial breast cancer. | Troudi W | Cancer biomarkers : section A of Disease markers | 2008 | PMID: 18334730 |
| Contribution of the BRCA1 and BRCA2 mutations to breast cancer in Tunisia. | Troudi W | Journal of human genetics | 2007 | PMID: 17922257 |
| Founder mutations in BRCA1 and BRCA2 genes. | Ferla R | Annals of oncology : official journal of the European Society for Medical Oncology | 2007 | PMID: 17591843 |
| Cancer risks in carriers of the BRCA1/2 Ashkenazi founder mutations. | Kadouri L | Journal of medical genetics | 2007 | PMID: 17307836 |
| BRCA1-positive breast cancers in young women from Poland. | Lubiński J | Breast cancer research and treatment | 2006 | PMID: 16541315 |
| Differences in the characteristics of families with BRCA1 and BRCA2 mutations in Israel. | Rennert G | European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) | 2005 | PMID: 16030426 |
| Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies. | Antoniou AC | Journal of medical genetics | 2005 | PMID: 15994883 |
| High prevalence of two BRCA1 mutations, 4154delA and 5382insC, in Latvia. | Tikhomirova L | Familial cancer | 2005 | PMID: 15951956 |
| Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. | Clapperton JA | Nature structural & molecular biology | 2004 | PMID: 15133502 |
| BRCA1 and BRCA2 mutations in women with familial or early-onset breast/ovarian cancer in the Czech Republic. | Foretova L | Human mutation | 2004 | PMID: 15024741 |
| Cytoplasmic mislocalization of BRCA1 caused by cancer-associated mutations in the BRCT domain. | Rodriguez JA | Experimental cell research | 2004 | PMID: 14729053 |
| Frequency of three BRCA1 gene founder mutations in breast/ovarian cancer families from the Pomerania-Kujawy region of Poland. | Janiszewska H | Clinical genetics | 2003 | PMID: 14986830 |
| Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. | King MC | Science (New York, N.Y.) | 2003 | PMID: 14576434 |
| Increased risk of breast cancer in relatives of malignant melanoma patients from families with strong cancer familial aggregation. | Debniak T | European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) | 2003 | PMID: 12771565 |
| Atypical medullary breast carcinoma in a family carrying the 5382insC BRCA-1 mutation. | Kroupis C | The breast journal | 2003 | PMID: 12752644 |
| A low frequency of non-founder BRCA1 mutations in Ashkenazi Jewish breast-ovarian cancer families. | Phelan CM | Human mutation | 2002 | PMID: 12402332 |
| Germ line BRCA1 & BRCA2 mutations in Greek breast/ovarian cancer families: 5382insC is the most frequent mutation observed. | Ladopoulou A | Cancer letters | 2002 | PMID: 12142080 |
| Analysis of 5382insC (BRCA1) and 6174delT (BRCA2) mutations in 382 healthy Chilean women with a family history of breast cancer. | Jara L | Biological research | 2002 | PMID: 12125210 |
| Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. | Frank TS | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2002 | PMID: 11896095 |
| Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population. | Meindl A | International journal of cancer | 2002 | PMID: 11802209 |
| Large regional differences in the frequency of distinct BRCA1/BRCA2 mutations in 517 Dutch breast and/or ovarian cancer families. | Verhoog LC | European journal of cancer (Oxford, England : 1990) | 2001 | PMID: 11597388 |
| The frequency of founder mutations in the BRCA1, BRCA2, and APC genes in Australian Ashkenazi Jews: implications for the generality of U.S. population data. | Bahar AY | Cancer | 2001 | PMID: 11466700 |
| Significantly lower rates of BRCA1/BRCA2 founder mutations in Ashkenazi women with sporadic compared with familial early onset breast cancer. | Gershoni-Baruch R | European journal of cancer (Oxford, England : 1990) | 2000 | PMID: 10885601 |
| Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer. | Górski B | American journal of human genetics | 2000 | PMID: 10788334 |
| BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. | Moslehi R | American journal of human genetics | 2000 | PMID: 10739756 |
| Strong founder effects in BRCA1 mutation carrier breast cancer patients from Latvia. Mutation in brief no. 258. Online. | Csokay B | Human mutation | 1999 | PMID: 10447273 |
| The prevalence of common BRCA1 and BRCA2 mutations among Ashkenazi Jews. | Hartge P | American journal of human genetics | 1999 | PMID: 10090881 |
| Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients. | Fodor FH | American journal of human genetics | 1998 | PMID: 9634504 |
| BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and ovarian cancer. | Schubert EL | Genetic testing | 1997 | PMID: 10464624 |
| Founder BRCA1 and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families. | Levy-Lahad E | American journal of human genetics | 1997 | PMID: 9150153 |
| The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. | Struewing JP | The New England journal of medicine | 1997 | PMID: 9145676 |
| The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women. | Abeliovich D | American journal of human genetics | 1997 | PMID: 9042909 |
| Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. | Roa BB | Nature genetics | 1996 | PMID: 8841191 |
| Genetic mapping of the Brca1 gene on mouse chromosome 11. | DeGregorio L | Mammalian genome : official journal of the International Mammalian Genome Society | 1996 | PMID: 8833256 |
| Rapid detection of regionally clustered germ-line BRCA1 mutations by multiplex heteroduplex analysis. UKCCCR Familial Ovarian Cancer Study Group. | Gayther SA | American journal of human genetics | 1996 | PMID: 8644703 |
| BRCA1 mutations in a population-based sample of young women with breast cancer. | Langston AA | The New England journal of medicine | 1996 | PMID: 8531967 |
| Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families. | Simard J | Nature genetics | 1994 | PMID: 7894492 |
| A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. | Miki Y | Science (New York, N.Y.) | 1994 | PMID: 7545954 |
| Konstantopoulou et al, Hu Mut 2000 | - | - | - | - |
| Wagner et al. Int. J. Cancer, in press | - | - | - | - |
| click to load more click to collapse | ||||
Text-mined citations for rs80357906 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.