Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.2433del (p.Lys812fs)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Sep 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.2433del (p.Lys812fs)
Variation ID: 37469 Accession: VCV000037469.44
- Type and length
-
Deletion, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43093098 (GRCh38) [ NCBI UCSC ] 17: 41245115 (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 19, 2014 Oct 8, 2024 Sep 8, 2016 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.2433del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Lys812fs frameshift NM_001407571.1:c.2220del NP_001394500.1:p.Lys741fs frameshift NM_001407581.1:c.2433del NP_001394510.1:p.Lys812fs frameshift NM_001407582.1:c.2433del NP_001394511.1:p.Lys812fs frameshift NM_001407583.1:c.2433del NP_001394512.1:p.Lys812fs frameshift NM_001407585.1:c.2433del NP_001394514.1:p.Lys812fs frameshift NM_001407587.1:c.2430del NP_001394516.1:p.Lys811fs frameshift NM_001407590.1:c.2430del NP_001394519.1:p.Lys811fs frameshift NM_001407591.1:c.2430del NP_001394520.1:p.Lys811fs frameshift NM_001407593.1:c.2433del NP_001394522.1:p.Lys812fs frameshift NM_001407594.1:c.2433del NP_001394523.1:p.Lys812fs frameshift NM_001407596.1:c.2433del NP_001394525.1:p.Lys812fs frameshift NM_001407597.1:c.2433del NP_001394526.1:p.Lys812fs frameshift NM_001407598.1:c.2433del NP_001394527.1:p.Lys812fs frameshift NM_001407602.1:c.2433del NP_001394531.1:p.Lys812fs frameshift NM_001407603.1:c.2433del NP_001394532.1:p.Lys812fs frameshift NM_001407605.1:c.2433del NP_001394534.1:p.Lys812fs frameshift NM_001407610.1:c.2430del NP_001394539.1:p.Lys811fs frameshift NM_001407611.1:c.2430del NP_001394540.1:p.Lys811fs frameshift NM_001407612.1:c.2430del NP_001394541.1:p.Lys811fs frameshift NM_001407613.1:c.2430del NP_001394542.1:p.Lys811fs frameshift NM_001407614.1:c.2430del NP_001394543.1:p.Lys811fs frameshift NM_001407615.1:c.2430del NP_001394544.1:p.Lys811fs frameshift NM_001407616.1:c.2433del NP_001394545.1:p.Lys812fs frameshift NM_001407617.1:c.2433del NP_001394546.1:p.Lys812fs frameshift NM_001407618.1:c.2433del NP_001394547.1:p.Lys812fs frameshift NM_001407619.1:c.2433del NP_001394548.1:p.Lys812fs frameshift NM_001407620.1:c.2433del NP_001394549.1:p.Lys812fs frameshift NM_001407621.1:c.2433del NP_001394550.1:p.Lys812fs frameshift NM_001407622.1:c.2433del NP_001394551.1:p.Lys812fs frameshift NM_001407623.1:c.2433del NP_001394552.1:p.Lys812fs frameshift NM_001407624.1:c.2433del NP_001394553.1:p.Lys812fs frameshift NM_001407625.1:c.2433del NP_001394554.1:p.Lys812fs frameshift NM_001407626.1:c.2433del NP_001394555.1:p.Lys812fs frameshift NM_001407627.1:c.2430del NP_001394556.1:p.Lys811fs frameshift NM_001407628.1:c.2430del NP_001394557.1:p.Lys811fs frameshift NM_001407629.1:c.2430del NP_001394558.1:p.Lys811fs frameshift NM_001407630.1:c.2430del NP_001394559.1:p.Lys811fs frameshift NM_001407631.1:c.2430del NP_001394560.1:p.Lys811fs frameshift NM_001407632.1:c.2430del NP_001394561.1:p.Lys811fs frameshift NM_001407633.1:c.2430del NP_001394562.1:p.Lys811fs frameshift NM_001407634.1:c.2430del NP_001394563.1:p.Lys811fs frameshift NM_001407635.1:c.2430del NP_001394564.1:p.Lys811fs frameshift NM_001407636.1:c.2430del NP_001394565.1:p.Lys811fs frameshift NM_001407637.1:c.2430del NP_001394566.1:p.Lys811fs frameshift NM_001407638.1:c.2430del NP_001394567.1:p.Lys811fs frameshift NM_001407639.1:c.2433del NP_001394568.1:p.Lys812fs frameshift NM_001407640.1:c.2433del NP_001394569.1:p.Lys812fs frameshift NM_001407641.1:c.2433del NP_001394570.1:p.Lys812fs frameshift NM_001407642.1:c.2433del NP_001394571.1:p.Lys812fs frameshift NM_001407644.1:c.2430del NP_001394573.1:p.Lys811fs frameshift NM_001407645.1:c.2430del NP_001394574.1:p.Lys811fs frameshift NM_001407646.1:c.2424del NP_001394575.1:p.Lys809fs frameshift NM_001407647.1:c.2424del NP_001394576.1:p.Lys809fs frameshift NM_001407648.1:c.2310del NP_001394577.1:p.Lys771fs frameshift NM_001407649.1:c.2307del NP_001394578.1:p.Lys770fs frameshift NM_001407652.1:c.2433del NP_001394581.1:p.Lys812fs frameshift NM_001407653.1:c.2355del NP_001394582.1:p.Lys786fs frameshift NM_001407654.1:c.2355del NP_001394583.1:p.Lys786fs frameshift NM_001407655.1:c.2355del NP_001394584.1:p.Lys786fs frameshift NM_001407656.1:c.2355del NP_001394585.1:p.Lys786fs frameshift NM_001407657.1:c.2355del NP_001394586.1:p.Lys786fs frameshift NM_001407658.1:c.2355del NP_001394587.1:p.Lys786fs frameshift NM_001407659.1:c.2352del NP_001394588.1:p.Lys785fs frameshift NM_001407660.1:c.2352del NP_001394589.1:p.Lys785fs frameshift NM_001407661.1:c.2352del NP_001394590.1:p.Lys785fs frameshift NM_001407662.1:c.2352del NP_001394591.1:p.Lys785fs frameshift NM_001407663.1:c.2355del NP_001394592.1:p.Lys786fs frameshift NM_001407664.1:c.2310del NP_001394593.1:p.Lys771fs frameshift NM_001407665.1:c.2310del NP_001394594.1:p.Lys771fs frameshift NM_001407666.1:c.2310del NP_001394595.1:p.Lys771fs frameshift NM_001407667.1:c.2310del NP_001394596.1:p.Lys771fs frameshift NM_001407668.1:c.2310del NP_001394597.1:p.Lys771fs frameshift NM_001407669.1:c.2310del NP_001394598.1:p.Lys771fs frameshift NM_001407670.1:c.2307del NP_001394599.1:p.Lys770fs frameshift NM_001407671.1:c.2307del NP_001394600.1:p.Lys770fs frameshift NM_001407672.1:c.2307del NP_001394601.1:p.Lys770fs frameshift NM_001407673.1:c.2307del NP_001394602.1:p.Lys770fs frameshift NM_001407674.1:c.2310del NP_001394603.1:p.Lys771fs frameshift NM_001407675.1:c.2310del NP_001394604.1:p.Lys771fs frameshift NM_001407676.1:c.2310del NP_001394605.1:p.Lys771fs frameshift NM_001407677.1:c.2310del NP_001394606.1:p.Lys771fs frameshift NM_001407678.1:c.2310del NP_001394607.1:p.Lys771fs frameshift NM_001407679.1:c.2310del NP_001394608.1:p.Lys771fs frameshift NM_001407680.1:c.2310del NP_001394609.1:p.Lys771fs frameshift NM_001407681.1:c.2310del NP_001394610.1:p.Lys771fs frameshift NM_001407682.1:c.2310del NP_001394611.1:p.Lys771fs frameshift NM_001407683.1:c.2310del NP_001394612.1:p.Lys771fs frameshift NM_001407684.1:c.2433del NP_001394613.1:p.Lys812fs frameshift NM_001407685.1:c.2307del NP_001394614.1:p.Lys770fs frameshift NM_001407686.1:c.2307del NP_001394615.1:p.Lys770fs frameshift NM_001407687.1:c.2307del NP_001394616.1:p.Lys770fs frameshift NM_001407688.1:c.2307del NP_001394617.1:p.Lys770fs frameshift NM_001407689.1:c.2307del NP_001394618.1:p.Lys770fs frameshift NM_001407690.1:c.2307del NP_001394619.1:p.Lys770fs frameshift NM_001407691.1:c.2307del NP_001394620.1:p.Lys770fs frameshift NM_001407692.1:c.2292del NP_001394621.1:p.Lys765fs frameshift NM_001407694.1:c.2292del NP_001394623.1:p.Lys765fs frameshift NM_001407695.1:c.2292del NP_001394624.1:p.Lys765fs frameshift NM_001407696.1:c.2292del NP_001394625.1:p.Lys765fs frameshift NM_001407697.1:c.2292del NP_001394626.1:p.Lys765fs frameshift NM_001407698.1:c.2292del NP_001394627.1:p.Lys765fs frameshift NM_001407724.1:c.2292del NP_001394653.1:p.Lys765fs frameshift NM_001407725.1:c.2292del NP_001394654.1:p.Lys765fs frameshift NM_001407726.1:c.2292del NP_001394655.1:p.Lys765fs frameshift NM_001407727.1:c.2292del NP_001394656.1:p.Lys765fs frameshift NM_001407728.1:c.2292del NP_001394657.1:p.Lys765fs frameshift NM_001407729.1:c.2292del NP_001394658.1:p.Lys765fs frameshift NM_001407730.1:c.2292del NP_001394659.1:p.Lys765fs frameshift NM_001407731.1:c.2292del NP_001394660.1:p.Lys765fs frameshift NM_001407732.1:c.2292del NP_001394661.1:p.Lys765fs frameshift NM_001407733.1:c.2292del NP_001394662.1:p.Lys765fs frameshift NM_001407734.1:c.2292del NP_001394663.1:p.Lys765fs frameshift NM_001407735.1:c.2292del NP_001394664.1:p.Lys765fs frameshift NM_001407736.1:c.2292del NP_001394665.1:p.Lys765fs frameshift NM_001407737.1:c.2292del NP_001394666.1:p.Lys765fs frameshift NM_001407738.1:c.2292del NP_001394667.1:p.Lys765fs frameshift NM_001407739.1:c.2292del NP_001394668.1:p.Lys765fs frameshift NM_001407740.1:c.2289del NP_001394669.1:p.Lys764fs frameshift NM_001407741.1:c.2289del NP_001394670.1:p.Lys764fs frameshift NM_001407742.1:c.2289del NP_001394671.1:p.Lys764fs frameshift NM_001407743.1:c.2289del NP_001394672.1:p.Lys764fs frameshift NM_001407744.1:c.2289del NP_001394673.1:p.Lys764fs frameshift NM_001407745.1:c.2289del NP_001394674.1:p.Lys764fs frameshift NM_001407746.1:c.2289del NP_001394675.1:p.Lys764fs frameshift NM_001407747.1:c.2289del NP_001394676.1:p.Lys764fs frameshift NM_001407748.1:c.2289del NP_001394677.1:p.Lys764fs frameshift NM_001407749.1:c.2289del NP_001394678.1:p.Lys764fs frameshift NM_001407750.1:c.2292del NP_001394679.1:p.Lys765fs frameshift NM_001407751.1:c.2292del NP_001394680.1:p.Lys765fs frameshift NM_001407752.1:c.2292del NP_001394681.1:p.Lys765fs frameshift NM_001407838.1:c.2289del NP_001394767.1:p.Lys764fs frameshift NM_001407839.1:c.2289del NP_001394768.1:p.Lys764fs frameshift NM_001407841.1:c.2289del NP_001394770.1:p.Lys764fs frameshift NM_001407842.1:c.2289del NP_001394771.1:p.Lys764fs frameshift NM_001407843.1:c.2289del NP_001394772.1:p.Lys764fs frameshift NM_001407844.1:c.2289del NP_001394773.1:p.Lys764fs frameshift NM_001407845.1:c.2289del NP_001394774.1:p.Lys764fs frameshift NM_001407846.1:c.2289del NP_001394775.1:p.Lys764fs frameshift NM_001407847.1:c.2289del NP_001394776.1:p.Lys764fs frameshift NM_001407848.1:c.2289del NP_001394777.1:p.Lys764fs frameshift NM_001407849.1:c.2289del NP_001394778.1:p.Lys764fs frameshift NM_001407850.1:c.2292del NP_001394779.1:p.Lys765fs frameshift NM_001407851.1:c.2292del NP_001394780.1:p.Lys765fs frameshift NM_001407852.1:c.2292del NP_001394781.1:p.Lys765fs frameshift NM_001407853.1:c.2220del NP_001394782.1:p.Lys741fs frameshift NM_001407854.1:c.2433del NP_001394783.1:p.Lys812fs frameshift NM_001407858.1:c.2433del NP_001394787.1:p.Lys812fs frameshift NM_001407859.1:c.2433del NP_001394788.1:p.Lys812fs frameshift NM_001407860.1:c.2430del NP_001394789.1:p.Lys811fs frameshift NM_001407861.1:c.2430del NP_001394790.1:p.Lys811fs frameshift NM_001407862.1:c.2232del NP_001394791.1:p.Lys745fs frameshift NM_001407863.1:c.2310del NP_001394792.1:p.Lys771fs frameshift NM_001407874.1:c.2229del NP_001394803.1:p.Lys744fs frameshift NM_001407875.1:c.2229del NP_001394804.1:p.Lys744fs frameshift NM_001407879.1:c.2223del NP_001394808.1:p.Lys742fs frameshift NM_001407881.1:c.2223del NP_001394810.1:p.Lys742fs frameshift NM_001407882.1:c.2223del NP_001394811.1:p.Lys742fs frameshift NM_001407884.1:c.2223del NP_001394813.1:p.Lys742fs frameshift NM_001407885.1:c.2223del NP_001394814.1:p.Lys742fs frameshift NM_001407886.1:c.2223del NP_001394815.1:p.Lys742fs frameshift NM_001407887.1:c.2223del NP_001394816.1:p.Lys742fs frameshift NM_001407889.1:c.2223del NP_001394818.1:p.Lys742fs frameshift NM_001407894.1:c.2220del NP_001394823.1:p.Lys741fs frameshift NM_001407895.1:c.2220del NP_001394824.1:p.Lys741fs frameshift NM_001407896.1:c.2220del NP_001394825.1:p.Lys741fs frameshift NM_001407897.1:c.2220del NP_001394826.1:p.Lys741fs frameshift NM_001407898.1:c.2220del NP_001394827.1:p.Lys741fs frameshift NM_001407899.1:c.2220del NP_001394828.1:p.Lys741fs frameshift NM_001407900.1:c.2223del NP_001394829.1:p.Lys742fs frameshift NM_001407902.1:c.2223del NP_001394831.1:p.Lys742fs frameshift NM_001407904.1:c.2223del NP_001394833.1:p.Lys742fs frameshift NM_001407906.1:c.2223del NP_001394835.1:p.Lys742fs frameshift NM_001407907.1:c.2223del NP_001394836.1:p.Lys742fs frameshift NM_001407908.1:c.2223del NP_001394837.1:p.Lys742fs frameshift NM_001407909.1:c.2223del NP_001394838.1:p.Lys742fs frameshift NM_001407910.1:c.2223del NP_001394839.1:p.Lys742fs frameshift NM_001407915.1:c.2220del NP_001394844.1:p.Lys741fs frameshift NM_001407916.1:c.2220del NP_001394845.1:p.Lys741fs frameshift NM_001407917.1:c.2220del NP_001394846.1:p.Lys741fs frameshift NM_001407918.1:c.2220del NP_001394847.1:p.Lys741fs frameshift NM_001407919.1:c.2310del NP_001394848.1:p.Lys771fs frameshift NM_001407920.1:c.2169del NP_001394849.1:p.Lys724fs frameshift NM_001407921.1:c.2169del NP_001394850.1:p.Lys724fs frameshift NM_001407922.1:c.2169del NP_001394851.1:p.Lys724fs frameshift NM_001407923.1:c.2169del NP_001394852.1:p.Lys724fs frameshift NM_001407924.1:c.2169del NP_001394853.1:p.Lys724fs frameshift NM_001407925.1:c.2169del NP_001394854.1:p.Lys724fs frameshift NM_001407926.1:c.2169del NP_001394855.1:p.Lys724fs frameshift NM_001407927.1:c.2169del NP_001394856.1:p.Lys724fs frameshift NM_001407928.1:c.2169del NP_001394857.1:p.Lys724fs frameshift NM_001407929.1:c.2169del NP_001394858.1:p.Lys724fs frameshift NM_001407930.1:c.2166del NP_001394859.1:p.Lys723fs frameshift NM_001407931.1:c.2166del NP_001394860.1:p.Lys723fs frameshift NM_001407932.1:c.2166del NP_001394861.1:p.Lys723fs frameshift NM_001407933.1:c.2169del NP_001394862.1:p.Lys724fs frameshift NM_001407934.1:c.2166del NP_001394863.1:p.Lys723fs frameshift NM_001407935.1:c.2169del NP_001394864.1:p.Lys724fs frameshift NM_001407936.1:c.2166del NP_001394865.1:p.Lys723fs frameshift NM_001407937.1:c.2310del NP_001394866.1:p.Lys771fs frameshift NM_001407938.1:c.2310del NP_001394867.1:p.Lys771fs frameshift NM_001407939.1:c.2310del NP_001394868.1:p.Lys771fs frameshift NM_001407940.1:c.2307del NP_001394869.1:p.Lys770fs frameshift NM_001407941.1:c.2307del NP_001394870.1:p.Lys770fs frameshift NM_001407942.1:c.2292del NP_001394871.1:p.Lys765fs frameshift NM_001407943.1:c.2289del NP_001394872.1:p.Lys764fs frameshift NM_001407944.1:c.2292del NP_001394873.1:p.Lys765fs frameshift NM_001407945.1:c.2292del NP_001394874.1:p.Lys765fs frameshift NM_001407946.1:c.2100del NP_001394875.1:p.Lys701fs frameshift NM_001407947.1:c.2100del NP_001394876.1:p.Lys701fs frameshift NM_001407948.1:c.2100del NP_001394877.1:p.Lys701fs frameshift NM_001407949.1:c.2100del NP_001394878.1:p.Lys701fs frameshift NM_001407950.1:c.2100del NP_001394879.1:p.Lys701fs frameshift NM_001407951.1:c.2100del NP_001394880.1:p.Lys701fs frameshift NM_001407952.1:c.2100del NP_001394881.1:p.Lys701fs frameshift NM_001407953.1:c.2100del NP_001394882.1:p.Lys701fs frameshift NM_001407954.1:c.2097del NP_001394883.1:p.Lys700fs frameshift NM_001407955.1:c.2097del NP_001394884.1:p.Lys700fs frameshift NM_001407956.1:c.2097del NP_001394885.1:p.Lys700fs frameshift NM_001407957.1:c.2100del NP_001394886.1:p.Lys701fs frameshift NM_001407958.1:c.2097del NP_001394887.1:p.Lys700fs frameshift NM_001407959.1:c.2052del NP_001394888.1:p.Lys685fs frameshift NM_001407960.1:c.2052del NP_001394889.1:p.Lys685fs frameshift NM_001407962.1:c.2049del NP_001394891.1:p.Lys684fs frameshift NM_001407963.1:c.2052del NP_001394892.1:p.Lys685fs frameshift NM_001407964.1:c.2289del NP_001394893.1:p.Lys764fs frameshift NM_001407965.1:c.1929del NP_001394894.1:p.Lys644fs frameshift NM_001407966.1:c.1545del NP_001394895.1:p.Lys516fs frameshift NM_001407967.1:c.1545del NP_001394896.1:p.Lys516fs frameshift NM_001407968.1:c.788-959del intron variant NM_001407969.1:c.788-959del intron variant NM_001407970.1:c.787+1646del intron variant NM_001407971.1:c.787+1646del intron variant NM_001407972.1:c.784+1646del intron variant NM_001407973.1:c.787+1646del intron variant NM_001407974.1:c.787+1646del intron variant NM_001407975.1:c.787+1646del intron variant NM_001407976.1:c.787+1646del intron variant NM_001407977.1:c.787+1646del intron variant NM_001407978.1:c.787+1646del intron variant NM_001407979.1:c.787+1646del intron variant NM_001407980.1:c.787+1646del intron variant NM_001407981.1:c.787+1646del intron variant NM_001407982.1:c.787+1646del intron variant NM_001407983.1:c.787+1646del intron variant NM_001407984.1:c.784+1646del intron variant NM_001407985.1:c.784+1646del intron variant NM_001407986.1:c.784+1646del intron variant NM_001407990.1:c.787+1646del intron variant NM_001407991.1:c.784+1646del intron variant NM_001407992.1:c.784+1646del intron variant NM_001407993.1:c.787+1646del intron variant NM_001408392.1:c.784+1646del intron variant NM_001408396.1:c.784+1646del intron variant NM_001408397.1:c.784+1646del intron variant NM_001408398.1:c.784+1646del intron variant NM_001408399.1:c.784+1646del intron variant NM_001408400.1:c.784+1646del intron variant NM_001408401.1:c.784+1646del intron variant NM_001408402.1:c.784+1646del intron variant NM_001408403.1:c.787+1646del intron variant NM_001408404.1:c.787+1646del intron variant NM_001408406.1:c.790+1643del intron variant NM_001408407.1:c.784+1646del intron variant NM_001408408.1:c.778+1646del intron variant NM_001408409.1:c.709+1646del intron variant NM_001408410.1:c.646+1646del intron variant NM_001408411.1:c.709+1646del intron variant NM_001408412.1:c.709+1646del intron variant NM_001408413.1:c.706+1646del intron variant NM_001408414.1:c.709+1646del intron variant NM_001408415.1:c.709+1646del intron variant NM_001408416.1:c.706+1646del intron variant NM_001408418.1:c.671-2066del intron variant NM_001408419.1:c.671-2066del intron variant NM_001408420.1:c.671-2066del intron variant NM_001408421.1:c.668-2066del intron variant NM_001408422.1:c.671-2066del intron variant NM_001408423.1:c.671-2066del intron variant NM_001408424.1:c.668-2066del intron variant NM_001408425.1:c.664+1646del intron variant NM_001408426.1:c.664+1646del intron variant NM_001408427.1:c.664+1646del intron variant NM_001408428.1:c.664+1646del intron variant NM_001408429.1:c.664+1646del intron variant NM_001408430.1:c.664+1646del intron variant NM_001408431.1:c.668-2066del intron variant NM_001408432.1:c.661+1646del intron variant NM_001408433.1:c.661+1646del intron variant NM_001408434.1:c.661+1646del intron variant NM_001408435.1:c.661+1646del intron variant NM_001408436.1:c.664+1646del intron variant NM_001408437.1:c.664+1646del intron variant NM_001408438.1:c.664+1646del intron variant NM_001408439.1:c.664+1646del intron variant NM_001408440.1:c.664+1646del intron variant NM_001408441.1:c.664+1646del intron variant NM_001408442.1:c.664+1646del intron variant NM_001408443.1:c.664+1646del intron variant NM_001408444.1:c.664+1646del intron variant NM_001408445.1:c.661+1646del intron variant NM_001408446.1:c.661+1646del intron variant NM_001408447.1:c.661+1646del intron variant NM_001408448.1:c.661+1646del intron variant NM_001408450.1:c.661+1646del intron variant NM_001408451.1:c.652+1646del intron variant NM_001408452.1:c.646+1646del intron variant NM_001408453.1:c.646+1646del intron variant NM_001408454.1:c.646+1646del intron variant NM_001408455.1:c.646+1646del intron variant NM_001408456.1:c.646+1646del intron variant NM_001408457.1:c.646+1646del intron variant NM_001408458.1:c.646+1646del intron variant NM_001408459.1:c.646+1646del intron variant NM_001408460.1:c.646+1646del intron variant NM_001408461.1:c.646+1646del intron variant NM_001408462.1:c.643+1646del intron variant NM_001408463.1:c.643+1646del intron variant NM_001408464.1:c.643+1646del intron variant NM_001408465.1:c.643+1646del intron variant NM_001408466.1:c.646+1646del intron variant NM_001408467.1:c.646+1646del intron variant NM_001408468.1:c.643+1646del intron variant NM_001408469.1:c.646+1646del intron variant NM_001408470.1:c.643+1646del intron variant NM_001408472.1:c.787+1646del intron variant NM_001408473.1:c.784+1646del intron variant NM_001408474.1:c.586+1646del intron variant NM_001408475.1:c.583+1646del intron variant NM_001408476.1:c.586+1646del intron variant NM_001408478.1:c.577+1646del intron variant NM_001408479.1:c.577+1646del intron variant NM_001408480.1:c.577+1646del intron variant NM_001408481.1:c.577+1646del intron variant NM_001408482.1:c.577+1646del intron variant NM_001408483.1:c.577+1646del intron variant NM_001408484.1:c.577+1646del intron variant NM_001408485.1:c.577+1646del intron variant NM_001408489.1:c.577+1646del intron variant NM_001408490.1:c.574+1646del intron variant NM_001408491.1:c.574+1646del intron variant NM_001408492.1:c.577+1646del intron variant NM_001408493.1:c.574+1646del intron variant NM_001408494.1:c.548-2066del intron variant NM_001408495.1:c.545-2066del intron variant NM_001408496.1:c.523+1646del intron variant NM_001408497.1:c.523+1646del intron variant NM_001408498.1:c.523+1646del intron variant NM_001408499.1:c.523+1646del intron variant NM_001408500.1:c.523+1646del intron variant NM_001408501.1:c.523+1646del intron variant NM_001408502.1:c.454+1646del intron variant NM_001408503.1:c.520+1646del intron variant NM_001408504.1:c.520+1646del intron variant NM_001408505.1:c.520+1646del intron variant NM_001408506.1:c.461-2066del intron variant NM_001408507.1:c.461-2066del intron variant NM_001408508.1:c.451+1646del intron variant NM_001408509.1:c.451+1646del intron variant NM_001408510.1:c.406+1646del intron variant NM_001408511.1:c.404-2066del intron variant NM_001408512.1:c.283+1646del intron variant NM_001408513.1:c.577+1646del intron variant NM_001408514.1:c.577+1646del intron variant NM_007294.3:c.2433delC frameshift NM_007297.4:c.2292del NP_009228.2:p.Lys765fs frameshift NM_007298.4:c.787+1646del intron variant NM_007299.4:c.787+1646del intron variant NM_007300.4:c.2433del NP_009231.2:p.Lys812fs frameshift NR_027676.1:n.2566delC NC_000017.11:g.43093101del NC_000017.10:g.41245118del NG_005905.2:g.124886del LRG_292:g.124886del LRG_292t1:c.2430del LRG_292p1:p.Lys812Argfs U14680.1:n.2552delC - Protein change
- K812fs, K765fs, K516fs, K684fs, K764fs, K771fs, K644fs, K701fs, K723fs, K786fs, K811fs, K700fs, K741fs, K742fs, K770fs, K785fs, K809fs, K685fs, K724fs, K744fs, K745fs
- Other names
-
2552delC
- Canonical SPDI
- NC_000017.11:43093097:GGGG:GGG
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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 (10) |
reviewed by expert panel
|
Sep 8, 2016 | RCV000031050.25 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 30, 2024 | RCV000047838.28 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Dec 27, 2022 | RCV000129993.20 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Sep 25, 2023 | RCV000236325.24 | |
| Pathogenic (1) |
no assertion criteria provided
|
- | RCV001353521.10 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Dec 8, 2021 | RCV002496472.8 | |
|
BRCA1-related disorder
|
Pathogenic (1) |
no assertion criteria provided
|
Apr 23, 2024 | RCV004758605.1 |
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
(Sep 08, 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: SCV000299767.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
Pathogenic
(Jun 10, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296330.7
First in ClinVar: Oct 19, 2014 Last updated: Jan 06, 2024 |
Comment:
This variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. In the published literature, this … (more)
This variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. In the published literature, this variant has been reported in individuals with breast and/or ovarian cancer (PMIDs: 30350268 (2018), 29240602 (2018), 23233716 (2013), 22217648 (2012), 20104584 (2010)). The frequency of this variant in the general population, 0.000008 (2/250608 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. (less)
|
|
|
Pathogenic
(Sep 25, 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: SCV001474266.2
First in ClinVar: Jan 26, 2021 Last updated: Feb 20, 2024 |
Comment:
The BRCA1 c.2433del; p.Lys812ArgfsTer3 variant (rs80357524), also reported as 2552delC, has been described in multiple individuals affected with breast and/or ovarian cancer and is a … (more)
The BRCA1 c.2433del; p.Lys812ArgfsTer3 variant (rs80357524), also reported as 2552delC, has been described in multiple individuals affected with breast and/or ovarian cancer and is a recurrent variant in Hispanic and Korean populations (Ahn 2007, Kim 2012, Tung 2015, Vogel 2007, Weitzel 2005). It is reported as a pathogenic variant by multiple sources in ClinVar (Variation ID: 37469) and is described on only 2 alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting 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 pathogenic. REFERENCES Ahn S et al. BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations. Cancer Lett. 2007 Jan 8;245(1-2):90-5. Kim H et al. Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer. Breast Cancer Res Treat. 2012 Aug;134(3):1315-26. Tung N et al. Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. Cancer. 2015 Jan 1;121(1):25-33. Vogel K et al. BRCA1 and BRCA2 genetic testing in Hispanic patients: mutation prevalence and evaluation of the BRCAPRO risk assessment model. J Clin Oncol. 2007 Oct 10;25(29):4635-41. Weitzel J et al. Prevalence of BRCA mutations and founder effect in high-risk Hispanic families. Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1666-71. (less)
|
|
|
Pathogenic
(Jun 29, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1
Affected status: yes
Allele origin:
germline
|
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV000996164.1
First in ClinVar: Oct 20, 2019 Last updated: Oct 20, 2019 |
Comment:
This frameshifting variant in exon 10 of 24 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function. … (more)
This frameshifting variant in exon 10 of 24 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function. This variant has been previously reported as a heterozygous change in multiple individuals with a personal or family history of breast and/or ovarian cancer (PMID: 25863477, 16455195, 25371446, 23233716). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.0008% (2/245,372) and thus is presumed to be rare. Based on the available evidence, the c.2433delC (p.Lys812ArgfsTer3) variant is classified as pathogenic. (less)
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Sep 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000292512.10
First in ClinVar: Jul 24, 2016 Last updated: Sep 30, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Truncating … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay 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; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 2552delC; This variant is associated with the following publications: (PMID: 22798144, 25628955, 20104584, 29673794, 34490083, 29922827, 28888541, 23233716, 19241424, 17591843, 17100994, 16949048, 16455195, 16030099, 19499246, 25863477, 16685647, 22217648, 19967274, 25371446, 26402875, 28985766, 26295337, 30350268, 30309222, 17925560, 16267036, 30274973, 30720243, 32868804, 28111427, 34645131) (less)
|
|
|
Pathogenic
(Mar 19, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004212692.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Jun 26, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000916767.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: BRCA1 c.2433delC (p.Lys812ArgfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA1 c.2433delC (p.Lys812ArgfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8.1e-06 in 245706 control chromosomes (gnomAD). The variant, c.2433delC, has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Han_2006, Weitzel_2005, Lim_2009, Vogel_2007, John_2007, Mgbemena_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
|
Pathogenic
(Jun 11, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Division of Medical Genetics, University of Washington
Study: CSER_CHARM
Accession: SCV001434307.1 First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Comment:
This variant causes a frameshift that leads to a premature termination codon. This variant is predicted to cause loss of normal protein either through protein … (more)
This variant causes a frameshift that leads to a premature termination codon. This variant is predicted to cause loss of normal protein either through protein truncation or nonsense-mediated mRNA decay. This variant has been reported in a number of women with breast and/or ovarian cancer (Ahn et al. 2007; Torres-Mejia et al. 2015; and Weitzel et al. 2013). Based on this evidence we interpret this variant as pathogenic. PS4; PVS1 (less)
Indication for testing: Personal and family history of breast cancer
|
|
|
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: SCV001519670.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Number of individuals with the variant: 2
Age: 42-45 years
Sex: female
Geographic origin: Tunisia
|
|
|
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: SCV000325356.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
|
|
Pathogenic
(Jul 05, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000488851.2
First in ClinVar: Nov 05, 2016 Last updated: Dec 24, 2022 |
|
|
|
Pathogenic
(Dec 08, 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: SCV002777467.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Pathogenic
(Sep 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV002819196.1
First in ClinVar: Jan 15, 2023 Last updated: Jan 15, 2023 |
|
|
|
Pathogenic
(Dec 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000911074.4
First in ClinVar: May 19, 2019 Last updated: Feb 14, 2024 |
Comment:
This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in over 10 individuals affected with breast and ovarian cancer (PMID: 16030099, 16685647, 16949048, 16455195, 17925560, 18159056, 19499246, 20104584, 22798144, 25186627, 25371446, 26402875, 33471991, 34063308) and has been observed to be a recurrent mutation in Latino and Korean populations (PMID: 17925560, 22798144, 26402875). This variant has been identified in 2/250608 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
|
|
|
Pathogenic
(Jan 30, 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: SCV000075851.14
First in ClinVar: Jul 03, 2013 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Lys812Argfs*3) in the BRCA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Lys812Argfs*3) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357524, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 16030099, 22798144, 23233716). This variant is also known as 2552delC. ClinVar contains an entry for this variant (Variation ID: 37469). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(May 11, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000184817.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The c.2433delC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 2433, causing … (more)
The c.2433delC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 2433, causing a translational frameshift with a predicted alternate stop codon (p.K812Rfs*3). This mutation has been reported in numerous HBOC patients and families (Weitzel JN et al. Cancer Epidemiol. Biomarkers Prev., 2005 Jul;14:1666-71; Kim BY et al. Biochem Biophys Res Commun, 2006 Oct;349:604-10; Han SH et al. Clin Genet, 2006 Dec;70:496-501; Ahn SH et al. Cancer Lett, 2007 Jan;245:90-5; Vogel KJ et al. J Clin Oncol, 2007 Oct;25:4635-41; John EM et al. JAMA, 2007 Dec;298:2869-76; Hall MJ et al. Cancer, 2009 May;115:2222-33; Lim MC et al. J Cancer Res Clin Oncol, 2009 Nov;135:1593-9; Borg A et al. Hum Mutat, 2010 Mar;31:E1200-40; Jang JH et al. J. Hum. Genet., 2012 Mar;57:212-5; Kim H et al. Breast Cancer Res Treat, 2012 Aug;134:1315-26; Weitzel JN et al. J Clin Oncol, 2013 Jan;31:210-6; Tung N et al. Cancer, 2015 Jan;121:25-33; Torres-Mejía G et al, 2015 Mar;24:498-505; Kang E et al. Breast Cancer Res Treat, 2015 May;151:157-68; Choi MC et al. Int J Gynecol Cancer, 2015 Oct;25:1386-91; Nahleh Z et al. Am J Cancer Res, 2015 Dec;5:466-71; Park JS et al. Cancer Res Treat, 2017 Oct;49:1012-1021; Ryu JM et al. Breast Cancer Res Treat, 2019 Jan;173:385-395; Dorling et al. N Engl J Med. 2021 02;384:428-439). This mutation has also been reported in patients with pancreatic cancer and acute myeloid leukemia (Bannon SA et al. Cancer Prev Res (Phila), 2018 11;11:679-686; Kim B et al. Sci Rep, 2020 08;10:14297). Of note, this alteration is also designated as 2552delC in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
|
|
|
Pathogenic
(Apr 23, 2024)
|
no assertion criteria provided
Method: clinical testing
|
BRCA1-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000806916.2
First in ClinVar: Sep 28, 2017 Last updated: Oct 08, 2024 |
Comment:
The BRCA1 c.2433delC variant is predicted to result in a frameshift and premature protein termination (p.Pro811Profs*4). This variant has been reported to be causative for … (more)
The BRCA1 c.2433delC variant is predicted to result in a frameshift and premature protein termination (p.Pro811Profs*4). This variant has been reported to be causative for Hereditary Breast and Ovarian Cancer syndrome (HBOC) (Kim et al. 2012. PubMed ID: 22798144; Weitzel et al. 2005. PubMed ID: 16030099). This variant (also known as c.2552delC) has been reported in at least 10 individuals (including 8 individuals from the Breast Cancer Information Core database) all of Hispanic origin with a family history of breast and ovarian cancers (Weitzel et al. 2005 PubMed ID: 16030099). This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD and has been interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/37469/). Frameshift variants in BRCA1 are expected to be pathogenic. 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: SCV000189892.1
First in ClinVar: Oct 19, 2014 Last updated: Oct 19, 2014 |
|
|
|
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: SCV000144435.2
First in ClinVar: Apr 01, 2014 Last updated: Oct 19, 2014 |
Observation 1:
Number of individuals with the variant: 2
Observation 2:
Number of individuals with the variant: 8
Ethnicity/Population group: Latin American, Caribbean
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: American
|
|
|
Pathogenic
(Jan 29, 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: SCV000053644.5
First in ClinVar: Apr 04, 2013 Last updated: Oct 19, 2014 |
|
|
|
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: SCV000587217.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
|
|
|
Pathogenic
(-)
|
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: SCV000591388.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The BRCA1 p.Lys812ArgfsX3 deletion variant was identified in at least 13 of 117374 proband chromosomes (frequency: 0.0001) from individuals or families with breast or ovarian … (more)
The BRCA1 p.Lys812ArgfsX3 deletion variant was identified in at least 13 of 117374 proband chromosomes (frequency: 0.0001) from individuals or families with breast or ovarian cancer, and was not identified in 334 control chromosomes from healthy individuals (Borg 2010, Han 2006, Judkins 2005, Weber 2006, Weitzel 2005). The variant was also identified in dbSNP (ID: rs80357524 ) “With pathogenic allele, HGMD, LOVD, COSMIC, the ClinVar database (classified as a pathogenic variant by the Sharing Clinical Reports Project (derived from Myriad reports); classified as pathogenic by Ambry Genetics), the BIC database (11X with clinical importance, classified as pathogenic), and UMD (1X as a causal variant). The p.Lys812ArgfsX3deletion variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 812 and leads to a premature stop codon 3 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as pathogenic. (less)
Number of individuals with the variant: 1
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
This variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. In the published literature, this variant has been reported in individuals with breast and/or ovarian cancer (PMIDs: 30350268 (2018), 29240602 (2018), 23233716 (2013), 22217648 (2012), 20104584 (2010)). The frequency of this variant in the general population, 0.000008 (2/250608 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic.
Comment:
The BRCA1 c.2433del; p.Lys812ArgfsTer3 variant (rs80357524), also reported as 2552delC, has been described in multiple individuals affected with breast and/or ovarian cancer and is a recurrent variant in Hispanic and Korean populations (Ahn 2007, Kim 2012, Tung 2015, Vogel 2007, Weitzel 2005). It is reported as a pathogenic variant by multiple sources in ClinVar (Variation ID: 37469) and is described on only 2 alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting 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 pathogenic. REFERENCES Ahn S et al. BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations. Cancer Lett. 2007 Jan 8;245(1-2):90-5. Kim H et al. Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer. Breast Cancer Res Treat. 2012 Aug;134(3):1315-26. Tung N et al. Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. Cancer. 2015 Jan 1;121(1):25-33. Vogel K et al. BRCA1 and BRCA2 genetic testing in Hispanic patients: mutation prevalence and evaluation of the BRCAPRO risk assessment model. J Clin Oncol. 2007 Oct 10;25(29):4635-41. Weitzel J et al. Prevalence of BRCA mutations and founder effect in high-risk Hispanic families. Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1666-71.
Comment:
This frameshifting variant in exon 10 of 24 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function. This variant has been previously reported as a heterozygous change in multiple individuals with a personal or family history of breast and/or ovarian cancer (PMID: 25863477, 16455195, 25371446, 23233716). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.0008% (2/245,372) and thus is presumed to be rare. Based on the available evidence, the c.2433delC (p.Lys812ArgfsTer3) variant is classified as pathogenic.
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay 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; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 2552delC; This variant is associated with the following publications: (PMID: 22798144, 25628955, 20104584, 29673794, 34490083, 29922827, 28888541, 23233716, 19241424, 17591843, 17100994, 16949048, 16455195, 16030099, 19499246, 25863477, 16685647, 22217648, 19967274, 25371446, 26402875, 28985766, 26295337, 30350268, 30309222, 17925560, 16267036, 30274973, 30720243, 32868804, 28111427, 34645131)
Comment:
Variant summary: BRCA1 c.2433delC (p.Lys812ArgfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8.1e-06 in 245706 control chromosomes (gnomAD). The variant, c.2433delC, has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Han_2006, Weitzel_2005, Lim_2009, Vogel_2007, John_2007, Mgbemena_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This variant causes a frameshift that leads to a premature termination codon. This variant is predicted to cause loss of normal protein either through protein truncation or nonsense-mediated mRNA decay. This variant has been reported in a number of women with breast and/or ovarian cancer (Ahn et al. 2007; Torres-Mejia et al. 2015; and Weitzel et al. 2013). Based on this evidence we interpret this variant as pathogenic. PS4; PVS1
Comment:
This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in over 10 individuals affected with breast and ovarian cancer (PMID: 16030099, 16685647, 16949048, 16455195, 17925560, 18159056, 19499246, 20104584, 22798144, 25186627, 25371446, 26402875, 33471991, 34063308) and has been observed to be a recurrent mutation in Latino and Korean populations (PMID: 17925560, 22798144, 26402875). This variant has been identified in 2/250608 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Lys812Argfs*3) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357524, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 16030099, 22798144, 23233716). This variant is also known as 2552delC. ClinVar contains an entry for this variant (Variation ID: 37469). For these reasons, this variant has been classified as Pathogenic.
Comment:
The c.2433delC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 2433, causing a translational frameshift with a predicted alternate stop codon (p.K812Rfs*3). This mutation has been reported in numerous HBOC patients and families (Weitzel JN et al. Cancer Epidemiol. Biomarkers Prev., 2005 Jul;14:1666-71; Kim BY et al. Biochem Biophys Res Commun, 2006 Oct;349:604-10; Han SH et al. Clin Genet, 2006 Dec;70:496-501; Ahn SH et al. Cancer Lett, 2007 Jan;245:90-5; Vogel KJ et al. J Clin Oncol, 2007 Oct;25:4635-41; John EM et al. JAMA, 2007 Dec;298:2869-76; Hall MJ et al. Cancer, 2009 May;115:2222-33; Lim MC et al. J Cancer Res Clin Oncol, 2009 Nov;135:1593-9; Borg A et al. Hum Mutat, 2010 Mar;31:E1200-40; Jang JH et al. J. Hum. Genet., 2012 Mar;57:212-5; Kim H et al. Breast Cancer Res Treat, 2012 Aug;134:1315-26; Weitzel JN et al. J Clin Oncol, 2013 Jan;31:210-6; Tung N et al. Cancer, 2015 Jan;121:25-33; Torres-Mejía G et al, 2015 Mar;24:498-505; Kang E et al. Breast Cancer Res Treat, 2015 May;151:157-68; Choi MC et al. Int J Gynecol Cancer, 2015 Oct;25:1386-91; Nahleh Z et al. Am J Cancer Res, 2015 Dec;5:466-71; Park JS et al. Cancer Res Treat, 2017 Oct;49:1012-1021; Ryu JM et al. Breast Cancer Res Treat, 2019 Jan;173:385-395; Dorling et al. N Engl J Med. 2021 02;384:428-439). This mutation has also been reported in patients with pancreatic cancer and acute myeloid leukemia (Bannon SA et al. Cancer Prev Res (Phila), 2018 11;11:679-686; Kim B et al. Sci Rep, 2020 08;10:14297). Of note, this alteration is also designated as 2552delC in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
The BRCA1 c.2433delC variant is predicted to result in a frameshift and premature protein termination (p.Pro811Profs*4). This variant has been reported to be causative for Hereditary Breast and Ovarian Cancer syndrome (HBOC) (Kim et al. 2012. PubMed ID: 22798144; Weitzel et al. 2005. PubMed ID: 16030099). This variant (also known as c.2552delC) has been reported in at least 10 individuals (including 8 individuals from the Breast Cancer Information Core database) all of Hispanic origin with a family history of breast and ovarian cancers (Weitzel et al. 2005 PubMed ID: 16030099). This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD and has been interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/37469/). Frameshift variants in BRCA1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Comment:
The BRCA1 p.Lys812ArgfsX3 deletion variant was identified in at least 13 of 117374 proband chromosomes (frequency: 0.0001) from individuals or families with breast or ovarian cancer, and was not identified in 334 control chromosomes from healthy individuals (Borg 2010, Han 2006, Judkins 2005, Weber 2006, Weitzel 2005). The variant was also identified in dbSNP (ID: rs80357524 ) “With pathogenic allele, HGMD, LOVD, COSMIC, the ClinVar database (classified as a pathogenic variant by the Sharing Clinical Reports Project (derived from Myriad reports); classified as pathogenic by Ambry Genetics), the BIC database (11X with clinical importance, classified as pathogenic), and UMD (1X as a causal variant). The p.Lys812ArgfsX3deletion variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 812 and leads to a premature stop codon 3 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as pathogenic.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
This variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. In the published literature, this variant has been reported in individuals with breast and/or ovarian cancer (PMIDs: 30350268 (2018), 29240602 (2018), 23233716 (2013), 22217648 (2012), 20104584 (2010)). The frequency of this variant in the general population, 0.000008 (2/250608 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic.
Comment:
The BRCA1 c.2433del; p.Lys812ArgfsTer3 variant (rs80357524), also reported as 2552delC, has been described in multiple individuals affected with breast and/or ovarian cancer and is a recurrent variant in Hispanic and Korean populations (Ahn 2007, Kim 2012, Tung 2015, Vogel 2007, Weitzel 2005). It is reported as a pathogenic variant by multiple sources in ClinVar (Variation ID: 37469) and is described on only 2 alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting 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 pathogenic. REFERENCES Ahn S et al. BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations. Cancer Lett. 2007 Jan 8;245(1-2):90-5. Kim H et al. Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer. Breast Cancer Res Treat. 2012 Aug;134(3):1315-26. Tung N et al. Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. Cancer. 2015 Jan 1;121(1):25-33. Vogel K et al. BRCA1 and BRCA2 genetic testing in Hispanic patients: mutation prevalence and evaluation of the BRCAPRO risk assessment model. J Clin Oncol. 2007 Oct 10;25(29):4635-41. Weitzel J et al. Prevalence of BRCA mutations and founder effect in high-risk Hispanic families. Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1666-71.
Comment:
This frameshifting variant in exon 10 of 24 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function. This variant has been previously reported as a heterozygous change in multiple individuals with a personal or family history of breast and/or ovarian cancer (PMID: 25863477, 16455195, 25371446, 23233716). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.0008% (2/245,372) and thus is presumed to be rare. Based on the available evidence, the c.2433delC (p.Lys812ArgfsTer3) variant is classified as pathogenic.
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay 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; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 2552delC; This variant is associated with the following publications: (PMID: 22798144, 25628955, 20104584, 29673794, 34490083, 29922827, 28888541, 23233716, 19241424, 17591843, 17100994, 16949048, 16455195, 16030099, 19499246, 25863477, 16685647, 22217648, 19967274, 25371446, 26402875, 28985766, 26295337, 30350268, 30309222, 17925560, 16267036, 30274973, 30720243, 32868804, 28111427, 34645131)
Comment:
Variant summary: BRCA1 c.2433delC (p.Lys812ArgfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8.1e-06 in 245706 control chromosomes (gnomAD). The variant, c.2433delC, has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Han_2006, Weitzel_2005, Lim_2009, Vogel_2007, John_2007, Mgbemena_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This variant causes a frameshift that leads to a premature termination codon. This variant is predicted to cause loss of normal protein either through protein truncation or nonsense-mediated mRNA decay. This variant has been reported in a number of women with breast and/or ovarian cancer (Ahn et al. 2007; Torres-Mejia et al. 2015; and Weitzel et al. 2013). Based on this evidence we interpret this variant as pathogenic. PS4; PVS1
Comment:
This variant deletes 1 nucleotide in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in over 10 individuals affected with breast and ovarian cancer (PMID: 16030099, 16685647, 16949048, 16455195, 17925560, 18159056, 19499246, 20104584, 22798144, 25186627, 25371446, 26402875, 33471991, 34063308) and has been observed to be a recurrent mutation in Latino and Korean populations (PMID: 17925560, 22798144, 26402875). This variant has been identified in 2/250608 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Lys812Argfs*3) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357524, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 16030099, 22798144, 23233716). This variant is also known as 2552delC. ClinVar contains an entry for this variant (Variation ID: 37469). For these reasons, this variant has been classified as Pathogenic.
Comment:
The c.2433delC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 2433, causing a translational frameshift with a predicted alternate stop codon (p.K812Rfs*3). This mutation has been reported in numerous HBOC patients and families (Weitzel JN et al. Cancer Epidemiol. Biomarkers Prev., 2005 Jul;14:1666-71; Kim BY et al. Biochem Biophys Res Commun, 2006 Oct;349:604-10; Han SH et al. Clin Genet, 2006 Dec;70:496-501; Ahn SH et al. Cancer Lett, 2007 Jan;245:90-5; Vogel KJ et al. J Clin Oncol, 2007 Oct;25:4635-41; John EM et al. JAMA, 2007 Dec;298:2869-76; Hall MJ et al. Cancer, 2009 May;115:2222-33; Lim MC et al. J Cancer Res Clin Oncol, 2009 Nov;135:1593-9; Borg A et al. Hum Mutat, 2010 Mar;31:E1200-40; Jang JH et al. J. Hum. Genet., 2012 Mar;57:212-5; Kim H et al. Breast Cancer Res Treat, 2012 Aug;134:1315-26; Weitzel JN et al. J Clin Oncol, 2013 Jan;31:210-6; Tung N et al. Cancer, 2015 Jan;121:25-33; Torres-Mejía G et al, 2015 Mar;24:498-505; Kang E et al. Breast Cancer Res Treat, 2015 May;151:157-68; Choi MC et al. Int J Gynecol Cancer, 2015 Oct;25:1386-91; Nahleh Z et al. Am J Cancer Res, 2015 Dec;5:466-71; Park JS et al. Cancer Res Treat, 2017 Oct;49:1012-1021; Ryu JM et al. Breast Cancer Res Treat, 2019 Jan;173:385-395; Dorling et al. N Engl J Med. 2021 02;384:428-439). This mutation has also been reported in patients with pancreatic cancer and acute myeloid leukemia (Bannon SA et al. Cancer Prev Res (Phila), 2018 11;11:679-686; Kim B et al. Sci Rep, 2020 08;10:14297). Of note, this alteration is also designated as 2552delC in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
The BRCA1 c.2433delC variant is predicted to result in a frameshift and premature protein termination (p.Pro811Profs*4). This variant has been reported to be causative for Hereditary Breast and Ovarian Cancer syndrome (HBOC) (Kim et al. 2012. PubMed ID: 22798144; Weitzel et al. 2005. PubMed ID: 16030099). This variant (also known as c.2552delC) has been reported in at least 10 individuals (including 8 individuals from the Breast Cancer Information Core database) all of Hispanic origin with a family history of breast and ovarian cancers (Weitzel et al. 2005 PubMed ID: 16030099). This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD and has been interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/37469/). Frameshift variants in BRCA1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Comment:
The BRCA1 p.Lys812ArgfsX3 deletion variant was identified in at least 13 of 117374 proband chromosomes (frequency: 0.0001) from individuals or families with breast or ovarian cancer, and was not identified in 334 control chromosomes from healthy individuals (Borg 2010, Han 2006, Judkins 2005, Weber 2006, Weitzel 2005). The variant was also identified in dbSNP (ID: rs80357524 ) “With pathogenic allele, HGMD, LOVD, COSMIC, the ClinVar database (classified as a pathogenic variant by the Sharing Clinical Reports Project (derived from Myriad reports); classified as pathogenic by Ambry Genetics), the BIC database (11X with clinical importance, classified as pathogenic), and UMD (1X as a causal variant). The p.Lys812ArgfsX3deletion variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 812 and leads to a premature stop codon 3 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA1 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| A Population-Based Analysis of BRCA1/2 Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study. | Park KS | Cancers | 2021 | PMID: 34063308 |
| 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 |
| Prevalence and clinical implications of germline predisposition gene mutations in patients with acute myeloid leukemia. | Kim B | Scientific reports | 2020 | PMID: 32868804 |
| Prevalence and oncologic outcomes of BRCA 1/2 mutations in unselected triple-negative breast cancer patients in Korea. | Ryu JM | Breast cancer research and treatment | 2019 | PMID: 30350268 |
| High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early-Onset Pancreatic Cancer. | Bannon SA | Cancer prevention research (Philadelphia, Pa.) | 2018 | PMID: 30274973 |
| Unclassified Variants of BRCA1 and BRCA2 in Korean Patients With Ovarian Cancer. | Choi MC | International journal of gynecological cancer : official journal of the International Gynecological Cancer Society | 2018 | PMID: 29240602 |
| Distinct Brca1 Mutations Differentially Reduce Hematopoietic Stem Cell Function. | Mgbemena VE | Cell reports | 2017 | PMID: 28122244 |
| 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 |
| Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients: Finding Founder Mutations. | Choi MC | International journal of gynecological cancer : official journal of the International Gynecological Cancer Society | 2015 | PMID: 26402875 |
| The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) study. | Kang E | Breast cancer research and treatment | 2015 | PMID: 25863477 |
| Recurrent BRCA1 and BRCA2 mutations in Mexican women with breast cancer. | Torres-Mejía G | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2015 | PMID: 25371446 |
| Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. | Tung N | Cancer | 2015 | PMID: 25186627 |
| Clinical and pathological characteristics of Hispanic BRCA-associated breast cancers in the American-Mexican border city of El Paso, TX. | Nahleh Z | American journal of cancer research | 2014 | PMID: 25628955 |
| Prevalence and type of BRCA mutations in Hispanics undergoing genetic cancer risk assessment in the southwestern United States: a report from the Clinical Cancer Genetics Community Research Network. | Weitzel JN | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2013 | PMID: 23233716 |
| Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer. | Kim H | Breast cancer research and treatment | 2012 | PMID: 22798144 |
| Spectra of BRCA1 and BRCA2 mutations in Korean patients with breast cancer: the importance of whole-gene sequencing. | Jang JH | Journal of human genetics | 2012 | PMID: 22217648 |
| Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
| BRCA1 and BRCA2 germline mutations in Korean ovarian cancer patients. | Lim MC | Journal of cancer research and clinical oncology | 2009 | PMID: 19499246 |
| BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer. | Hall MJ | Cancer | 2009 | PMID: 19241424 |
| Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups. | John EM | JAMA | 2007 | PMID: 18159056 |
| BRCA1 and BRCA2 genetic testing in Hispanic patients: mutation prevalence and evaluation of the BRCAPRO risk assessment model. | Vogel KJ | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2007 | PMID: 17925560 |
| Founder mutations in BRCA1 and BRCA2 genes. | Ferla R | Annals of oncology : official journal of the European Society for Medical Oncology | 2007 | PMID: 17591843 |
| BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations. | Ahn SH | Cancer letters | 2007 | PMID: 16455195 |
| Mutation analysis of BRCA1 and BRCA2 from 793 Korean patients with sporadic breast cancer. | Han SH | Clinical genetics | 2006 | PMID: 17100994 |
| Identification of BRCA1 and BRCA2 mutations from Korean breast cancer patients using denaturing HPLC. | Kim BY | Biochemical and biophysical research communications | 2006 | PMID: 16949048 |
| Total-genome analysis of BRCA1/2-related invasive carcinomas of the breast identifies tumor stroma as potential landscaper for neoplastic initiation. | Weber F | American journal of human genetics | 2006 | PMID: 16685647 |
| Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. | Judkins T | Cancer research | 2005 | PMID: 16267036 |
| Prevalence of BRCA mutations and founder effect in high-risk Hispanic families. | Weitzel JN | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2005 | PMID: 16030099 |
| Relation of contraceptive and reproductive history to ovarian cancer risk in carriers and noncarriers of BRCA1 gene mutations. | McGuire V | American journal of epidemiology | 2004 | PMID: 15383404 |
| click to load more click to collapse | ||||
Text-mined citations for rs80357524 ...
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.