Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.2138C>G (p.Ser713Ter)
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
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NM_007294.4(BRCA1):c.2138C>G (p.Ser713Ter)
Variation ID: 37451 Accession: VCV000037451.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43093393 (GRCh38) [ NCBI UCSC ] 17: 41245410 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Sep 27, 2014 Sep 16, 2024 Sep 8, 2016 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.2138C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ser713Ter nonsense NM_001407571.1:c.1925C>G NP_001394500.1:p.Ser642Ter nonsense NM_001407581.1:c.2138C>G NP_001394510.1:p.Ser713Ter nonsense NM_001407582.1:c.2138C>G NP_001394511.1:p.Ser713Ter nonsense NM_001407583.1:c.2138C>G NP_001394512.1:p.Ser713Ter nonsense NM_001407585.1:c.2138C>G NP_001394514.1:p.Ser713Ter nonsense NM_001407587.1:c.2135C>G NP_001394516.1:p.Ser712Ter nonsense NM_001407590.1:c.2135C>G NP_001394519.1:p.Ser712Ter nonsense NM_001407591.1:c.2135C>G NP_001394520.1:p.Ser712Ter nonsense NM_001407593.1:c.2138C>G NP_001394522.1:p.Ser713Ter nonsense NM_001407594.1:c.2138C>G NP_001394523.1:p.Ser713Ter nonsense NM_001407596.1:c.2138C>G NP_001394525.1:p.Ser713Ter nonsense NM_001407597.1:c.2138C>G NP_001394526.1:p.Ser713Ter nonsense NM_001407598.1:c.2138C>G NP_001394527.1:p.Ser713Ter nonsense NM_001407602.1:c.2138C>G NP_001394531.1:p.Ser713Ter nonsense NM_001407603.1:c.2138C>G NP_001394532.1:p.Ser713Ter nonsense NM_001407605.1:c.2138C>G NP_001394534.1:p.Ser713Ter nonsense NM_001407610.1:c.2135C>G NP_001394539.1:p.Ser712Ter nonsense NM_001407611.1:c.2135C>G NP_001394540.1:p.Ser712Ter nonsense NM_001407612.1:c.2135C>G NP_001394541.1:p.Ser712Ter nonsense NM_001407613.1:c.2135C>G NP_001394542.1:p.Ser712Ter nonsense NM_001407614.1:c.2135C>G NP_001394543.1:p.Ser712Ter nonsense NM_001407615.1:c.2135C>G NP_001394544.1:p.Ser712Ter nonsense NM_001407616.1:c.2138C>G NP_001394545.1:p.Ser713Ter nonsense NM_001407617.1:c.2138C>G NP_001394546.1:p.Ser713Ter nonsense NM_001407618.1:c.2138C>G NP_001394547.1:p.Ser713Ter nonsense NM_001407619.1:c.2138C>G NP_001394548.1:p.Ser713Ter nonsense NM_001407620.1:c.2138C>G NP_001394549.1:p.Ser713Ter nonsense NM_001407621.1:c.2138C>G NP_001394550.1:p.Ser713Ter nonsense NM_001407622.1:c.2138C>G NP_001394551.1:p.Ser713Ter nonsense NM_001407623.1:c.2138C>G NP_001394552.1:p.Ser713Ter nonsense NM_001407624.1:c.2138C>G NP_001394553.1:p.Ser713Ter nonsense NM_001407625.1:c.2138C>G NP_001394554.1:p.Ser713Ter nonsense NM_001407626.1:c.2138C>G NP_001394555.1:p.Ser713Ter nonsense NM_001407627.1:c.2135C>G NP_001394556.1:p.Ser712Ter nonsense NM_001407628.1:c.2135C>G NP_001394557.1:p.Ser712Ter nonsense NM_001407629.1:c.2135C>G NP_001394558.1:p.Ser712Ter nonsense NM_001407630.1:c.2135C>G NP_001394559.1:p.Ser712Ter nonsense NM_001407631.1:c.2135C>G NP_001394560.1:p.Ser712Ter nonsense NM_001407632.1:c.2135C>G NP_001394561.1:p.Ser712Ter nonsense NM_001407633.1:c.2135C>G NP_001394562.1:p.Ser712Ter nonsense NM_001407634.1:c.2135C>G NP_001394563.1:p.Ser712Ter nonsense NM_001407635.1:c.2135C>G NP_001394564.1:p.Ser712Ter nonsense NM_001407636.1:c.2135C>G NP_001394565.1:p.Ser712Ter nonsense NM_001407637.1:c.2135C>G NP_001394566.1:p.Ser712Ter nonsense NM_001407638.1:c.2135C>G NP_001394567.1:p.Ser712Ter nonsense NM_001407639.1:c.2138C>G NP_001394568.1:p.Ser713Ter nonsense NM_001407640.1:c.2138C>G NP_001394569.1:p.Ser713Ter nonsense NM_001407641.1:c.2138C>G NP_001394570.1:p.Ser713Ter nonsense NM_001407642.1:c.2138C>G NP_001394571.1:p.Ser713Ter nonsense NM_001407644.1:c.2135C>G NP_001394573.1:p.Ser712Ter nonsense NM_001407645.1:c.2135C>G NP_001394574.1:p.Ser712Ter nonsense NM_001407646.1:c.2129C>G NP_001394575.1:p.Ser710Ter nonsense NM_001407647.1:c.2129C>G NP_001394576.1:p.Ser710Ter nonsense NM_001407648.1:c.2015C>G NP_001394577.1:p.Ser672Ter nonsense NM_001407649.1:c.2012C>G NP_001394578.1:p.Ser671Ter nonsense NM_001407652.1:c.2138C>G NP_001394581.1:p.Ser713Ter nonsense NM_001407653.1:c.2060C>G NP_001394582.1:p.Ser687Ter nonsense NM_001407654.1:c.2060C>G NP_001394583.1:p.Ser687Ter nonsense NM_001407655.1:c.2060C>G NP_001394584.1:p.Ser687Ter nonsense NM_001407656.1:c.2060C>G NP_001394585.1:p.Ser687Ter nonsense NM_001407657.1:c.2060C>G NP_001394586.1:p.Ser687Ter nonsense NM_001407658.1:c.2060C>G NP_001394587.1:p.Ser687Ter nonsense NM_001407659.1:c.2057C>G NP_001394588.1:p.Ser686Ter nonsense NM_001407660.1:c.2057C>G NP_001394589.1:p.Ser686Ter nonsense NM_001407661.1:c.2057C>G NP_001394590.1:p.Ser686Ter nonsense NM_001407662.1:c.2057C>G NP_001394591.1:p.Ser686Ter nonsense NM_001407663.1:c.2060C>G NP_001394592.1:p.Ser687Ter nonsense NM_001407664.1:c.2015C>G NP_001394593.1:p.Ser672Ter nonsense NM_001407665.1:c.2015C>G NP_001394594.1:p.Ser672Ter nonsense NM_001407666.1:c.2015C>G NP_001394595.1:p.Ser672Ter nonsense NM_001407667.1:c.2015C>G NP_001394596.1:p.Ser672Ter nonsense NM_001407668.1:c.2015C>G NP_001394597.1:p.Ser672Ter nonsense NM_001407669.1:c.2015C>G NP_001394598.1:p.Ser672Ter nonsense NM_001407670.1:c.2012C>G NP_001394599.1:p.Ser671Ter nonsense NM_001407671.1:c.2012C>G NP_001394600.1:p.Ser671Ter nonsense NM_001407672.1:c.2012C>G NP_001394601.1:p.Ser671Ter nonsense NM_001407673.1:c.2012C>G NP_001394602.1:p.Ser671Ter nonsense NM_001407674.1:c.2015C>G NP_001394603.1:p.Ser672Ter nonsense NM_001407675.1:c.2015C>G NP_001394604.1:p.Ser672Ter nonsense NM_001407676.1:c.2015C>G NP_001394605.1:p.Ser672Ter nonsense NM_001407677.1:c.2015C>G NP_001394606.1:p.Ser672Ter nonsense NM_001407678.1:c.2015C>G NP_001394607.1:p.Ser672Ter nonsense NM_001407679.1:c.2015C>G NP_001394608.1:p.Ser672Ter nonsense NM_001407680.1:c.2015C>G NP_001394609.1:p.Ser672Ter nonsense NM_001407681.1:c.2015C>G NP_001394610.1:p.Ser672Ter nonsense NM_001407682.1:c.2015C>G NP_001394611.1:p.Ser672Ter nonsense NM_001407683.1:c.2015C>G NP_001394612.1:p.Ser672Ter nonsense NM_001407684.1:c.2138C>G NP_001394613.1:p.Ser713Ter nonsense NM_001407685.1:c.2012C>G NP_001394614.1:p.Ser671Ter nonsense NM_001407686.1:c.2012C>G NP_001394615.1:p.Ser671Ter nonsense NM_001407687.1:c.2012C>G NP_001394616.1:p.Ser671Ter nonsense NM_001407688.1:c.2012C>G NP_001394617.1:p.Ser671Ter nonsense NM_001407689.1:c.2012C>G NP_001394618.1:p.Ser671Ter nonsense NM_001407690.1:c.2012C>G NP_001394619.1:p.Ser671Ter nonsense NM_001407691.1:c.2012C>G NP_001394620.1:p.Ser671Ter nonsense NM_001407692.1:c.1997C>G NP_001394621.1:p.Ser666Ter nonsense NM_001407694.1:c.1997C>G NP_001394623.1:p.Ser666Ter nonsense NM_001407695.1:c.1997C>G NP_001394624.1:p.Ser666Ter nonsense NM_001407696.1:c.1997C>G NP_001394625.1:p.Ser666Ter nonsense NM_001407697.1:c.1997C>G NP_001394626.1:p.Ser666Ter nonsense NM_001407698.1:c.1997C>G NP_001394627.1:p.Ser666Ter nonsense NM_001407724.1:c.1997C>G NP_001394653.1:p.Ser666Ter nonsense NM_001407725.1:c.1997C>G NP_001394654.1:p.Ser666Ter nonsense NM_001407726.1:c.1997C>G NP_001394655.1:p.Ser666Ter nonsense NM_001407727.1:c.1997C>G NP_001394656.1:p.Ser666Ter nonsense NM_001407728.1:c.1997C>G NP_001394657.1:p.Ser666Ter nonsense NM_001407729.1:c.1997C>G NP_001394658.1:p.Ser666Ter nonsense NM_001407730.1:c.1997C>G NP_001394659.1:p.Ser666Ter nonsense NM_001407731.1:c.1997C>G NP_001394660.1:p.Ser666Ter nonsense NM_001407732.1:c.1997C>G NP_001394661.1:p.Ser666Ter nonsense NM_001407733.1:c.1997C>G NP_001394662.1:p.Ser666Ter nonsense NM_001407734.1:c.1997C>G NP_001394663.1:p.Ser666Ter nonsense NM_001407735.1:c.1997C>G NP_001394664.1:p.Ser666Ter nonsense NM_001407736.1:c.1997C>G NP_001394665.1:p.Ser666Ter nonsense NM_001407737.1:c.1997C>G NP_001394666.1:p.Ser666Ter nonsense NM_001407738.1:c.1997C>G NP_001394667.1:p.Ser666Ter nonsense NM_001407739.1:c.1997C>G NP_001394668.1:p.Ser666Ter nonsense NM_001407740.1:c.1994C>G NP_001394669.1:p.Ser665Ter nonsense NM_001407741.1:c.1994C>G NP_001394670.1:p.Ser665Ter nonsense NM_001407742.1:c.1994C>G NP_001394671.1:p.Ser665Ter nonsense NM_001407743.1:c.1994C>G NP_001394672.1:p.Ser665Ter nonsense NM_001407744.1:c.1994C>G NP_001394673.1:p.Ser665Ter nonsense NM_001407745.1:c.1994C>G NP_001394674.1:p.Ser665Ter nonsense NM_001407746.1:c.1994C>G NP_001394675.1:p.Ser665Ter nonsense NM_001407747.1:c.1994C>G NP_001394676.1:p.Ser665Ter nonsense NM_001407748.1:c.1994C>G NP_001394677.1:p.Ser665Ter nonsense NM_001407749.1:c.1994C>G NP_001394678.1:p.Ser665Ter nonsense NM_001407750.1:c.1997C>G NP_001394679.1:p.Ser666Ter nonsense NM_001407751.1:c.1997C>G NP_001394680.1:p.Ser666Ter nonsense NM_001407752.1:c.1997C>G NP_001394681.1:p.Ser666Ter nonsense NM_001407838.1:c.1994C>G NP_001394767.1:p.Ser665Ter nonsense NM_001407839.1:c.1994C>G NP_001394768.1:p.Ser665Ter nonsense NM_001407841.1:c.1994C>G NP_001394770.1:p.Ser665Ter nonsense NM_001407842.1:c.1994C>G NP_001394771.1:p.Ser665Ter nonsense NM_001407843.1:c.1994C>G NP_001394772.1:p.Ser665Ter nonsense NM_001407844.1:c.1994C>G NP_001394773.1:p.Ser665Ter nonsense NM_001407845.1:c.1994C>G NP_001394774.1:p.Ser665Ter nonsense NM_001407846.1:c.1994C>G NP_001394775.1:p.Ser665Ter nonsense NM_001407847.1:c.1994C>G NP_001394776.1:p.Ser665Ter nonsense NM_001407848.1:c.1994C>G NP_001394777.1:p.Ser665Ter nonsense NM_001407849.1:c.1994C>G NP_001394778.1:p.Ser665Ter nonsense NM_001407850.1:c.1997C>G NP_001394779.1:p.Ser666Ter nonsense NM_001407851.1:c.1997C>G NP_001394780.1:p.Ser666Ter nonsense NM_001407852.1:c.1997C>G NP_001394781.1:p.Ser666Ter nonsense NM_001407853.1:c.1925C>G NP_001394782.1:p.Ser642Ter nonsense NM_001407854.1:c.2138C>G NP_001394783.1:p.Ser713Ter nonsense NM_001407858.1:c.2138C>G NP_001394787.1:p.Ser713Ter nonsense NM_001407859.1:c.2138C>G NP_001394788.1:p.Ser713Ter nonsense NM_001407860.1:c.2135C>G NP_001394789.1:p.Ser712Ter nonsense NM_001407861.1:c.2135C>G NP_001394790.1:p.Ser712Ter nonsense NM_001407862.1:c.1937C>G NP_001394791.1:p.Ser646Ter nonsense NM_001407863.1:c.2015C>G NP_001394792.1:p.Ser672Ter nonsense NM_001407874.1:c.1934C>G NP_001394803.1:p.Ser645Ter nonsense NM_001407875.1:c.1934C>G NP_001394804.1:p.Ser645Ter nonsense NM_001407879.1:c.1928C>G NP_001394808.1:p.Ser643Ter nonsense NM_001407881.1:c.1928C>G NP_001394810.1:p.Ser643Ter nonsense NM_001407882.1:c.1928C>G NP_001394811.1:p.Ser643Ter nonsense NM_001407884.1:c.1928C>G NP_001394813.1:p.Ser643Ter nonsense NM_001407885.1:c.1928C>G NP_001394814.1:p.Ser643Ter nonsense NM_001407886.1:c.1928C>G NP_001394815.1:p.Ser643Ter nonsense NM_001407887.1:c.1928C>G NP_001394816.1:p.Ser643Ter nonsense NM_001407889.1:c.1928C>G NP_001394818.1:p.Ser643Ter nonsense NM_001407894.1:c.1925C>G NP_001394823.1:p.Ser642Ter nonsense NM_001407895.1:c.1925C>G NP_001394824.1:p.Ser642Ter nonsense NM_001407896.1:c.1925C>G NP_001394825.1:p.Ser642Ter nonsense NM_001407897.1:c.1925C>G NP_001394826.1:p.Ser642Ter nonsense NM_001407898.1:c.1925C>G NP_001394827.1:p.Ser642Ter nonsense NM_001407899.1:c.1925C>G NP_001394828.1:p.Ser642Ter nonsense NM_001407900.1:c.1928C>G NP_001394829.1:p.Ser643Ter nonsense NM_001407902.1:c.1928C>G NP_001394831.1:p.Ser643Ter nonsense NM_001407904.1:c.1928C>G NP_001394833.1:p.Ser643Ter nonsense NM_001407906.1:c.1928C>G NP_001394835.1:p.Ser643Ter nonsense NM_001407907.1:c.1928C>G NP_001394836.1:p.Ser643Ter nonsense NM_001407908.1:c.1928C>G NP_001394837.1:p.Ser643Ter nonsense NM_001407909.1:c.1928C>G NP_001394838.1:p.Ser643Ter nonsense NM_001407910.1:c.1928C>G NP_001394839.1:p.Ser643Ter nonsense NM_001407915.1:c.1925C>G NP_001394844.1:p.Ser642Ter nonsense NM_001407916.1:c.1925C>G NP_001394845.1:p.Ser642Ter nonsense NM_001407917.1:c.1925C>G NP_001394846.1:p.Ser642Ter nonsense NM_001407918.1:c.1925C>G NP_001394847.1:p.Ser642Ter nonsense NM_001407919.1:c.2015C>G NP_001394848.1:p.Ser672Ter nonsense NM_001407920.1:c.1874C>G NP_001394849.1:p.Ser625Ter nonsense NM_001407921.1:c.1874C>G NP_001394850.1:p.Ser625Ter nonsense NM_001407922.1:c.1874C>G NP_001394851.1:p.Ser625Ter nonsense NM_001407923.1:c.1874C>G NP_001394852.1:p.Ser625Ter nonsense NM_001407924.1:c.1874C>G NP_001394853.1:p.Ser625Ter nonsense NM_001407925.1:c.1874C>G NP_001394854.1:p.Ser625Ter nonsense NM_001407926.1:c.1874C>G NP_001394855.1:p.Ser625Ter nonsense NM_001407927.1:c.1874C>G NP_001394856.1:p.Ser625Ter nonsense NM_001407928.1:c.1874C>G NP_001394857.1:p.Ser625Ter nonsense NM_001407929.1:c.1874C>G NP_001394858.1:p.Ser625Ter nonsense NM_001407930.1:c.1871C>G NP_001394859.1:p.Ser624Ter nonsense NM_001407931.1:c.1871C>G NP_001394860.1:p.Ser624Ter nonsense NM_001407932.1:c.1871C>G NP_001394861.1:p.Ser624Ter nonsense NM_001407933.1:c.1874C>G NP_001394862.1:p.Ser625Ter nonsense NM_001407934.1:c.1871C>G NP_001394863.1:p.Ser624Ter nonsense NM_001407935.1:c.1874C>G NP_001394864.1:p.Ser625Ter nonsense NM_001407936.1:c.1871C>G NP_001394865.1:p.Ser624Ter nonsense NM_001407937.1:c.2015C>G NP_001394866.1:p.Ser672Ter nonsense NM_001407938.1:c.2015C>G NP_001394867.1:p.Ser672Ter nonsense NM_001407939.1:c.2015C>G NP_001394868.1:p.Ser672Ter nonsense NM_001407940.1:c.2012C>G NP_001394869.1:p.Ser671Ter nonsense NM_001407941.1:c.2012C>G NP_001394870.1:p.Ser671Ter nonsense NM_001407942.1:c.1997C>G NP_001394871.1:p.Ser666Ter nonsense NM_001407943.1:c.1994C>G NP_001394872.1:p.Ser665Ter nonsense NM_001407944.1:c.1997C>G NP_001394873.1:p.Ser666Ter nonsense NM_001407945.1:c.1997C>G NP_001394874.1:p.Ser666Ter nonsense NM_001407946.1:c.1805C>G NP_001394875.1:p.Ser602Ter nonsense NM_001407947.1:c.1805C>G NP_001394876.1:p.Ser602Ter nonsense NM_001407948.1:c.1805C>G NP_001394877.1:p.Ser602Ter nonsense NM_001407949.1:c.1805C>G NP_001394878.1:p.Ser602Ter nonsense NM_001407950.1:c.1805C>G NP_001394879.1:p.Ser602Ter nonsense NM_001407951.1:c.1805C>G NP_001394880.1:p.Ser602Ter nonsense NM_001407952.1:c.1805C>G NP_001394881.1:p.Ser602Ter nonsense NM_001407953.1:c.1805C>G NP_001394882.1:p.Ser602Ter nonsense NM_001407954.1:c.1802C>G NP_001394883.1:p.Ser601Ter nonsense NM_001407955.1:c.1802C>G NP_001394884.1:p.Ser601Ter nonsense NM_001407956.1:c.1802C>G NP_001394885.1:p.Ser601Ter nonsense NM_001407957.1:c.1805C>G NP_001394886.1:p.Ser602Ter nonsense NM_001407958.1:c.1802C>G NP_001394887.1:p.Ser601Ter nonsense NM_001407959.1:c.1757C>G NP_001394888.1:p.Ser586Ter nonsense NM_001407960.1:c.1757C>G NP_001394889.1:p.Ser586Ter nonsense NM_001407962.1:c.1754C>G NP_001394891.1:p.Ser585Ter nonsense NM_001407963.1:c.1757C>G NP_001394892.1:p.Ser586Ter nonsense NM_001407964.1:c.1994C>G NP_001394893.1:p.Ser665Ter nonsense NM_001407965.1:c.1634C>G NP_001394894.1:p.Ser545Ter nonsense NM_001407966.1:c.1250C>G NP_001394895.1:p.Ser417Ter nonsense NM_001407967.1:c.1250C>G NP_001394896.1:p.Ser417Ter nonsense NM_001407968.1:c.788-1254C>G intron variant NM_001407969.1:c.788-1254C>G intron variant NM_001407970.1:c.787+1351C>G intron variant NM_001407971.1:c.787+1351C>G intron variant NM_001407972.1:c.784+1351C>G intron variant NM_001407973.1:c.787+1351C>G intron variant NM_001407974.1:c.787+1351C>G intron variant NM_001407975.1:c.787+1351C>G intron variant NM_001407976.1:c.787+1351C>G intron variant NM_001407977.1:c.787+1351C>G intron variant NM_001407978.1:c.787+1351C>G intron variant NM_001407979.1:c.787+1351C>G intron variant NM_001407980.1:c.787+1351C>G intron variant NM_001407981.1:c.787+1351C>G intron variant NM_001407982.1:c.787+1351C>G intron variant NM_001407983.1:c.787+1351C>G intron variant NM_001407984.1:c.784+1351C>G intron variant NM_001407985.1:c.784+1351C>G intron variant NM_001407986.1:c.784+1351C>G intron variant NM_001407990.1:c.787+1351C>G intron variant NM_001407991.1:c.784+1351C>G intron variant NM_001407992.1:c.784+1351C>G intron variant NM_001407993.1:c.787+1351C>G intron variant NM_001408392.1:c.784+1351C>G intron variant NM_001408396.1:c.784+1351C>G intron variant NM_001408397.1:c.784+1351C>G intron variant NM_001408398.1:c.784+1351C>G intron variant NM_001408399.1:c.784+1351C>G intron variant NM_001408400.1:c.784+1351C>G intron variant NM_001408401.1:c.784+1351C>G intron variant NM_001408402.1:c.784+1351C>G intron variant NM_001408403.1:c.787+1351C>G intron variant NM_001408404.1:c.787+1351C>G intron variant NM_001408406.1:c.790+1348C>G intron variant NM_001408407.1:c.784+1351C>G intron variant NM_001408408.1:c.778+1351C>G intron variant NM_001408409.1:c.709+1351C>G intron variant NM_001408410.1:c.646+1351C>G intron variant NM_001408411.1:c.709+1351C>G intron variant NM_001408412.1:c.709+1351C>G intron variant NM_001408413.1:c.706+1351C>G intron variant NM_001408414.1:c.709+1351C>G intron variant NM_001408415.1:c.709+1351C>G intron variant NM_001408416.1:c.706+1351C>G intron variant NM_001408418.1:c.671-2361C>G intron variant NM_001408419.1:c.671-2361C>G intron variant NM_001408420.1:c.671-2361C>G intron variant NM_001408421.1:c.668-2361C>G intron variant NM_001408422.1:c.671-2361C>G intron variant NM_001408423.1:c.671-2361C>G intron variant NM_001408424.1:c.668-2361C>G intron variant NM_001408425.1:c.664+1351C>G intron variant NM_001408426.1:c.664+1351C>G intron variant NM_001408427.1:c.664+1351C>G intron variant NM_001408428.1:c.664+1351C>G intron variant NM_001408429.1:c.664+1351C>G intron variant NM_001408430.1:c.664+1351C>G intron variant NM_001408431.1:c.668-2361C>G intron variant NM_001408432.1:c.661+1351C>G intron variant NM_001408433.1:c.661+1351C>G intron variant NM_001408434.1:c.661+1351C>G intron variant NM_001408435.1:c.661+1351C>G intron variant NM_001408436.1:c.664+1351C>G intron variant NM_001408437.1:c.664+1351C>G intron variant NM_001408438.1:c.664+1351C>G intron variant NM_001408439.1:c.664+1351C>G intron variant NM_001408440.1:c.664+1351C>G intron variant NM_001408441.1:c.664+1351C>G intron variant NM_001408442.1:c.664+1351C>G intron variant NM_001408443.1:c.664+1351C>G intron variant NM_001408444.1:c.664+1351C>G intron variant NM_001408445.1:c.661+1351C>G intron variant NM_001408446.1:c.661+1351C>G intron variant NM_001408447.1:c.661+1351C>G intron variant NM_001408448.1:c.661+1351C>G intron variant NM_001408450.1:c.661+1351C>G intron variant NM_001408451.1:c.652+1351C>G intron variant NM_001408452.1:c.646+1351C>G intron variant NM_001408453.1:c.646+1351C>G intron variant NM_001408454.1:c.646+1351C>G intron variant NM_001408455.1:c.646+1351C>G intron variant NM_001408456.1:c.646+1351C>G intron variant NM_001408457.1:c.646+1351C>G intron variant NM_001408458.1:c.646+1351C>G intron variant NM_001408459.1:c.646+1351C>G intron variant NM_001408460.1:c.646+1351C>G intron variant NM_001408461.1:c.646+1351C>G intron variant NM_001408462.1:c.643+1351C>G intron variant NM_001408463.1:c.643+1351C>G intron variant NM_001408464.1:c.643+1351C>G intron variant NM_001408465.1:c.643+1351C>G intron variant NM_001408466.1:c.646+1351C>G intron variant NM_001408467.1:c.646+1351C>G intron variant NM_001408468.1:c.643+1351C>G intron variant NM_001408469.1:c.646+1351C>G intron variant NM_001408470.1:c.643+1351C>G intron variant NM_001408472.1:c.787+1351C>G intron variant NM_001408473.1:c.784+1351C>G intron variant NM_001408474.1:c.586+1351C>G intron variant NM_001408475.1:c.583+1351C>G intron variant NM_001408476.1:c.586+1351C>G intron variant NM_001408478.1:c.577+1351C>G intron variant NM_001408479.1:c.577+1351C>G intron variant NM_001408480.1:c.577+1351C>G intron variant NM_001408481.1:c.577+1351C>G intron variant NM_001408482.1:c.577+1351C>G intron variant NM_001408483.1:c.577+1351C>G intron variant NM_001408484.1:c.577+1351C>G intron variant NM_001408485.1:c.577+1351C>G intron variant NM_001408489.1:c.577+1351C>G intron variant NM_001408490.1:c.574+1351C>G intron variant NM_001408491.1:c.574+1351C>G intron variant NM_001408492.1:c.577+1351C>G intron variant NM_001408493.1:c.574+1351C>G intron variant NM_001408494.1:c.548-2361C>G intron variant NM_001408495.1:c.545-2361C>G intron variant NM_001408496.1:c.523+1351C>G intron variant NM_001408497.1:c.523+1351C>G intron variant NM_001408498.1:c.523+1351C>G intron variant NM_001408499.1:c.523+1351C>G intron variant NM_001408500.1:c.523+1351C>G intron variant NM_001408501.1:c.523+1351C>G intron variant NM_001408502.1:c.454+1351C>G intron variant NM_001408503.1:c.520+1351C>G intron variant NM_001408504.1:c.520+1351C>G intron variant NM_001408505.1:c.520+1351C>G intron variant NM_001408506.1:c.461-2361C>G intron variant NM_001408507.1:c.461-2361C>G intron variant NM_001408508.1:c.451+1351C>G intron variant NM_001408509.1:c.451+1351C>G intron variant NM_001408510.1:c.406+1351C>G intron variant NM_001408511.1:c.404-2361C>G intron variant NM_001408512.1:c.283+1351C>G intron variant NM_001408513.1:c.577+1351C>G intron variant NM_001408514.1:c.577+1351C>G intron variant NM_007297.4:c.1997C>G NP_009228.2:p.Ser666Ter nonsense NM_007298.4:c.787+1351C>G intron variant NM_007299.4:c.787+1351C>G intron variant NM_007300.4:c.2138C>G NP_009231.2:p.Ser713Ter nonsense NR_027676.1:n.2274C>G NC_000017.11:g.43093393G>C NC_000017.10:g.41245410G>C NG_005905.2:g.124591C>G LRG_292:g.124591C>G LRG_292t1:c.2138C>G LRG_292p1:p.Ser713Ter U14680.1:n.2257C>G - Protein change
- S713*, S666*, S624*, S417*, S545*, S586*, S601*, S643*, S645*, S665*, S672*, S642*, S687*, S585*, S602*, S625*, S646*, S671*, S686*, S710*, S712*
- Other names
-
p.S713*:TCA>TGA
2257C>G
- Canonical SPDI
- NC_000017.11:43093392:G:C
-
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.
-
The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- 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 (8) |
reviewed by expert panel
|
Sep 8, 2016 | RCV000031032.25 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Jan 3, 2024 | RCV000047730.23 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Mar 28, 2024 | RCV000074571.26 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 16, 2023 | RCV000162851.19 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Apr 3, 2022 | RCV002477031.8 |
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: SCV000299705.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
Pathogenic
(Jan 18, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296379.5
First in ClinVar: Mar 20, 2016 Last updated: Jan 06, 2024 |
Comment:
This nonsense variant causes the premature termination of BRCA1 protein synthesis. It has been reported in families affected with breast/ovarian cancer in the published literature … (more)
This nonsense variant causes the premature termination of BRCA1 protein synthesis. It has been reported in families affected with breast/ovarian cancer in the published literature (PMID: 11139249 (2001), 29446198 (2018), 30702160 (2019)). Therefore, the variant is classified as pathogenic and this individual is at increased risk of developing BRCA1 related cancers. (less)
|
|
|
Pathogenic
(Nov 20, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV000266027.1
First in ClinVar: Mar 20, 2016 Last updated: Mar 20, 2016 |
Number of individuals with the variant: 1
Clinical Features:
ovarian cancer (present)
Age: 40-49 years
|
|
|
Pathogenic
(Nov 11, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004212688.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Oct 03, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000108656.16
First in ClinVar: Dec 10, 2013 Last updated: Sep 16, 2024 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense 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; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (PMID: 11139249, 22430266, 21913181, 25722380, 27469594, 30968603); 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 2257C>G; This variant is associated with the following publications: (PMID: 25400221, 32211327, 28888541, 25525159, 15829246, 26848529, 25722380, 21913181, 22430266, 11139249, 27150160, 27469594, 30702160, 30720243, 30968603, 29625052, 26689913, 32719484, 32341426, 31825140, 29339979, 30078507, 29446198, 28176296, 28724667, 35864222, 34981296, 36451132) (less)
|
|
|
Pathogenic
(Apr 21, 2016)
|
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: SCV000564388.1
First in ClinVar: Apr 22, 2017 Last updated: Apr 22, 2017 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Feb 16, 2017)
|
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: SCV000698921.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Comment:
Variant summary: The BRCA1 c.2138C>G (p.Ser713X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense … (more)
Variant summary: The BRCA1 c.2138C>G (p.Ser713X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.2157dupA. p.Glu720fsX6; c.2197_2201delGAGAA, p.Glu733fsX5; c.2241delC, p.Asp749fsX4). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/122388 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). The variant has been reported in numerous affected individuals in the literature. Functional studies have demonstrated a reduction on multiple aspects of BRCA1 function attributed to this variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. (less)
|
|
|
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: SCV000325263.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
|
|
Pathogenic
(Apr 03, 2022)
|
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: SCV002795346.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Pathogenic
(Apr 27, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003809746.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Jan 03, 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: SCV000075743.14
First in ClinVar: Jul 03, 2013 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ser713*) 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.Ser713*) 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 (rs80357233, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with a personal and/or family history of breast and ovarian cancer (PMID: 11139249, 21913181, 22430266). This variant is also known as 2257C>G. ClinVar contains an entry for this variant (Variation ID: 37451). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
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Pathogenic
(Mar 16, 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: SCV000911170.4
First in ClinVar: May 19, 2019 Last updated: Feb 14, 2024 |
Comment:
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in multiple individuals and families affected with breast and/or ovarian cancer (PMID: 11139249, 21913181, 22762150, 26845104, 28724667, 30702160, 31825140), and has been identified in 8 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant also has been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 0/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_001833). This variant has been identified in 2/282518 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
(Feb 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004818223.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in multiple individuals and families affected with breast and/or ovarian cancer (PMID: 11139249, 21913181, 22762150, 26845104, 28724667, 30702160, 31825140), and has been identified in 8 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant also has been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 0/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_001833). This variant has been identified in 2/282518 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)
Number of individuals with the variant: 3
|
|
|
Pathogenic
(Apr 29, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000213338.7
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The p.S713* pathogenic mutation (also known as c.2138C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at … (more)
The p.S713* pathogenic mutation (also known as c.2138C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 2138. This changes the amino acid from a serine to a stop codon within coding exon 9. This mutation was previously identified in individuals and families with breast and/or ovarian cancer diagnoses (Vaziri SA et al. Hum. Mutat. 2001;17:74; Sun J et al. Clin. Cancer Res. 2017 Oct;23:6113-6119; Shi T et al. Int. J. Cancer 2017 05;140:2051-2059; Bhaskaran SP et al. Int. J. Cancer 2019 Jan). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat. 2018 05;39:593-620). Of note, this alteration is also designated as 2257C>G 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
(Mar 28, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005199742.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
|
|
|
Pathogenic
(Nov 27, 2012)
|
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: SCV000053626.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
|
|
|
Pathogenic
(May 29, 2002)
|
no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline,
unknown
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144310.2
First in ClinVar: Apr 01, 2014 Last updated: Sep 27, 2014 |
Observation 1:
Number of individuals with the variant: 9
Observation 2:
Number of individuals with the variant: 1
Geographic origin: Western European
Observation 3:
Number of individuals with the variant: 7
Ethnicity/Population group: Western European
Observation 4:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Native American
Observation 5:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: American
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Pathogenic
(Jan 31, 2014)
|
no assertion criteria provided
Method: research
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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: SCV000587190.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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Comment:
Comment:
This nonsense variant causes the premature termination of BRCA1 protein synthesis. It has been reported in families affected with breast/ovarian cancer in the published literature (PMID: 11139249 (2001), 29446198 (2018), 30702160 (2019)). Therefore, the variant is classified as pathogenic and this individual is at increased risk of developing BRCA1 related cancers.
Comment:
Nonsense 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; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (PMID: 11139249, 22430266, 21913181, 25722380, 27469594, 30968603); 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 2257C>G; This variant is associated with the following publications: (PMID: 25400221, 32211327, 28888541, 25525159, 15829246, 26848529, 25722380, 21913181, 22430266, 11139249, 27150160, 27469594, 30702160, 30720243, 30968603, 29625052, 26689913, 32719484, 32341426, 31825140, 29339979, 30078507, 29446198, 28176296, 28724667, 35864222, 34981296, 36451132)
Comment:
Variant summary: The BRCA1 c.2138C>G (p.Ser713X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.2157dupA. p.Glu720fsX6; c.2197_2201delGAGAA, p.Glu733fsX5; c.2241delC, p.Asp749fsX4). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/122388 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). The variant has been reported in numerous affected individuals in the literature. Functional studies have demonstrated a reduction on multiple aspects of BRCA1 function attributed to this variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Ser713*) 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 (rs80357233, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with a personal and/or family history of breast and ovarian cancer (PMID: 11139249, 21913181, 22430266). This variant is also known as 2257C>G. ClinVar contains an entry for this variant (Variation ID: 37451). For these reasons, this variant has been classified as Pathogenic.
Comment:
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in multiple individuals and families affected with breast and/or ovarian cancer (PMID: 11139249, 21913181, 22762150, 26845104, 28724667, 30702160, 31825140), and has been identified in 8 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant also has been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 0/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_001833). This variant has been identified in 2/282518 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 variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in multiple individuals and families affected with breast and/or ovarian cancer (PMID: 11139249, 21913181, 22762150, 26845104, 28724667, 30702160, 31825140), and has been identified in 8 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant also has been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 0/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_001833). This variant has been identified in 2/282518 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:
The p.S713* pathogenic mutation (also known as c.2138C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 2138. This changes the amino acid from a serine to a stop codon within coding exon 9. This mutation was previously identified in individuals and families with breast and/or ovarian cancer diagnoses (Vaziri SA et al. Hum. Mutat. 2001;17:74; Sun J et al. Clin. Cancer Res. 2017 Oct;23:6113-6119; Shi T et al. Int. J. Cancer 2017 05;140:2051-2059; Bhaskaran SP et al. Int. J. Cancer 2019 Jan). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat. 2018 05;39:593-620). Of note, this alteration is also designated as 2257C>G 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.
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 nonsense variant causes the premature termination of BRCA1 protein synthesis. It has been reported in families affected with breast/ovarian cancer in the published literature (PMID: 11139249 (2001), 29446198 (2018), 30702160 (2019)). Therefore, the variant is classified as pathogenic and this individual is at increased risk of developing BRCA1 related cancers.
Comment:
Nonsense 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; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (PMID: 11139249, 22430266, 21913181, 25722380, 27469594, 30968603); 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 2257C>G; This variant is associated with the following publications: (PMID: 25400221, 32211327, 28888541, 25525159, 15829246, 26848529, 25722380, 21913181, 22430266, 11139249, 27150160, 27469594, 30702160, 30720243, 30968603, 29625052, 26689913, 32719484, 32341426, 31825140, 29339979, 30078507, 29446198, 28176296, 28724667, 35864222, 34981296, 36451132)
Comment:
Variant summary: The BRCA1 c.2138C>G (p.Ser713X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.2157dupA. p.Glu720fsX6; c.2197_2201delGAGAA, p.Glu733fsX5; c.2241delC, p.Asp749fsX4). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/122388 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). The variant has been reported in numerous affected individuals in the literature. Functional studies have demonstrated a reduction on multiple aspects of BRCA1 function attributed to this variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Ser713*) 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 (rs80357233, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with a personal and/or family history of breast and ovarian cancer (PMID: 11139249, 21913181, 22430266). This variant is also known as 2257C>G. ClinVar contains an entry for this variant (Variation ID: 37451). For these reasons, this variant has been classified as Pathogenic.
Comment:
This variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in multiple individuals and families affected with breast and/or ovarian cancer (PMID: 11139249, 21913181, 22762150, 26845104, 28724667, 30702160, 31825140), and has been identified in 8 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant also has been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 0/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_001833). This variant has been identified in 2/282518 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 variant changes 1 nucleotide in exon 10 of the BRCA1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in multiple individuals and families affected with breast and/or ovarian cancer (PMID: 11139249, 21913181, 22762150, 26845104, 28724667, 30702160, 31825140), and has been identified in 8 families among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant also has been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 0/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA1_001833). This variant has been identified in 2/282518 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:
The p.S713* pathogenic mutation (also known as c.2138C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 2138. This changes the amino acid from a serine to a stop codon within coding exon 9. This mutation was previously identified in individuals and families with breast and/or ovarian cancer diagnoses (Vaziri SA et al. Hum. Mutat. 2001;17:74; Sun J et al. Clin. Cancer Res. 2017 Oct;23:6113-6119; Shi T et al. Int. J. Cancer 2017 05;140:2051-2059; Bhaskaran SP et al. Int. J. Cancer 2019 Jan). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat. 2018 05;39:593-620). Of note, this alteration is also designated as 2257C>G 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.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
| Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients. | Gao X | Human mutation | 2020 | PMID: 31825140 |
| Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. | Bhaskaran SP | International journal of cancer | 2019 | PMID: 30702160 |
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients. | Sun J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 28724667 |
| BRCA1 and BRCA2 mutations in ovarian cancer patients from China: ethnic-related mutations in BRCA1 associated with an increased risk of ovarian cancer. | Shi T | International journal of cancer | 2017 | PMID: 28176296 |
| A Survey of BRCA1, BRCA2, and PALB2 mutations in women with breast cancer in Trinidad and Tobago. | Donenberg T | Breast cancer research and treatment | 2016 | PMID: 27469594 |
| Improving performance of multigene panels for genomic analysis of cancer predisposition. | Shirts BH | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26845104 |
| BRCA1 haploinsufficiency for replication stress suppression in primary cells. | Pathania S | Nature communications | 2014 | PMID: 25400221 |
| Integrated analysis of germline and somatic variants in ovarian cancer. | Kanchi KL | Nature communications | 2014 | PMID: 24448499 |
| Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO). | Lecarpentier J | Breast cancer research : BCR | 2012 | PMID: 22762150 |
| 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 |
| Earlier age of onset of BRCA mutation-related cancers in subsequent generations. | Litton JK | Cancer | 2012 | PMID: 21913181 |
| Prevalence and predictors of loss of wild type BRCA1 in estrogen receptor positive and negative BRCA1-associated breast cancers. | Tung N | Breast cancer research : BCR | 2010 | PMID: 21080930 |
| 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 |
| 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 |
| Single nucleotide polymorphisms in clinical genetic testing: the characterization of the clinical significance of genetic variants and their application in clinical research for BRCA1. | Judkins T | Mutation research | 2005 | PMID: 15829246 |
| 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 |
| Frequency of BRCA1 and BRCA2 mutations in a clinic-based series of breast and ovarian cancer families. | Vaziri SA | Human mutation | 2001 | PMID: 11139249 |
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Text-mined citations for rs80357233 ...
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.