ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5558A>G (p.Tyr1853Cys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5558A>G (p.Tyr1853Cys)
Variation ID: 55627 Accession: VCV000055627.35
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43045712 (GRCh38) [ NCBI UCSC ] 17: 41197729 (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 Apr 1, 2014 Feb 14, 2024 Nov 16, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.5558A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Tyr1853Cys missense NM_001407571.1:c.5345A>G NP_001394500.1:p.Tyr1782Cys missense NM_001407581.1:c.5624A>G NP_001394510.1:p.Tyr1875Cys missense NM_001407582.1:c.5624A>G NP_001394511.1:p.Tyr1875Cys missense NM_001407583.1:c.5621A>G NP_001394512.1:p.Tyr1874Cys missense NM_001407585.1:c.5621A>G NP_001394514.1:p.Tyr1874Cys missense NM_001407587.1:c.5621A>G NP_001394516.1:p.Tyr1874Cys missense NM_001407590.1:c.5618A>G NP_001394519.1:p.Tyr1873Cys missense NM_001407591.1:c.5618A>G NP_001394520.1:p.Tyr1873Cys missense NM_001407593.1:c.5558A>G NP_001394522.1:p.Tyr1853Cys missense NM_001407594.1:c.5558A>G NP_001394523.1:p.Tyr1853Cys missense NM_001407596.1:c.5558A>G NP_001394525.1:p.Tyr1853Cys missense NM_001407597.1:c.5558A>G NP_001394526.1:p.Tyr1853Cys missense NM_001407598.1:c.5558A>G NP_001394527.1:p.Tyr1853Cys missense NM_001407602.1:c.5558A>G NP_001394531.1:p.Tyr1853Cys missense NM_001407603.1:c.5558A>G NP_001394532.1:p.Tyr1853Cys missense NM_001407605.1:c.5558A>G NP_001394534.1:p.Tyr1853Cys missense NM_001407610.1:c.5555A>G NP_001394539.1:p.Tyr1852Cys missense NM_001407611.1:c.5555A>G NP_001394540.1:p.Tyr1852Cys missense NM_001407612.1:c.5555A>G NP_001394541.1:p.Tyr1852Cys missense NM_001407613.1:c.5555A>G NP_001394542.1:p.Tyr1852Cys missense NM_001407614.1:c.5555A>G NP_001394543.1:p.Tyr1852Cys missense NM_001407615.1:c.5555A>G NP_001394544.1:p.Tyr1852Cys missense NM_001407616.1:c.5555A>G NP_001394545.1:p.Tyr1852Cys missense NM_001407617.1:c.5555A>G NP_001394546.1:p.Tyr1852Cys missense NM_001407618.1:c.5555A>G NP_001394547.1:p.Tyr1852Cys missense NM_001407619.1:c.5555A>G NP_001394548.1:p.Tyr1852Cys missense NM_001407620.1:c.5555A>G NP_001394549.1:p.Tyr1852Cys missense NM_001407621.1:c.5555A>G NP_001394550.1:p.Tyr1852Cys missense NM_001407622.1:c.5555A>G NP_001394551.1:p.Tyr1852Cys missense NM_001407623.1:c.5555A>G NP_001394552.1:p.Tyr1852Cys missense NM_001407624.1:c.5555A>G NP_001394553.1:p.Tyr1852Cys missense NM_001407625.1:c.5555A>G NP_001394554.1:p.Tyr1852Cys missense NM_001407626.1:c.5555A>G NP_001394555.1:p.Tyr1852Cys missense NM_001407627.1:c.5552A>G NP_001394556.1:p.Tyr1851Cys missense NM_001407628.1:c.5552A>G NP_001394557.1:p.Tyr1851Cys missense NM_001407629.1:c.5552A>G NP_001394558.1:p.Tyr1851Cys missense NM_001407630.1:c.5552A>G NP_001394559.1:p.Tyr1851Cys missense NM_001407631.1:c.5552A>G NP_001394560.1:p.Tyr1851Cys missense NM_001407632.1:c.5552A>G NP_001394561.1:p.Tyr1851Cys missense NM_001407633.1:c.5552A>G NP_001394562.1:p.Tyr1851Cys missense NM_001407634.1:c.5552A>G NP_001394563.1:p.Tyr1851Cys missense NM_001407635.1:c.5552A>G NP_001394564.1:p.Tyr1851Cys missense NM_001407636.1:c.5552A>G NP_001394565.1:p.Tyr1851Cys missense NM_001407637.1:c.5552A>G NP_001394566.1:p.Tyr1851Cys missense NM_001407638.1:c.5552A>G NP_001394567.1:p.Tyr1851Cys missense NM_001407639.1:c.5552A>G NP_001394568.1:p.Tyr1851Cys missense NM_001407640.1:c.5552A>G NP_001394569.1:p.Tyr1851Cys missense NM_001407641.1:c.5552A>G NP_001394570.1:p.Tyr1851Cys missense NM_001407642.1:c.5552A>G NP_001394571.1:p.Tyr1851Cys missense NM_001407644.1:c.5549A>G NP_001394573.1:p.Tyr1850Cys missense NM_001407645.1:c.5549A>G NP_001394574.1:p.Tyr1850Cys missense NM_001407646.1:c.5546A>G NP_001394575.1:p.Tyr1849Cys missense NM_001407647.1:c.5543A>G NP_001394576.1:p.Tyr1848Cys missense NM_001407648.1:c.5501A>G NP_001394577.1:p.Tyr1834Cys missense NM_001407649.1:c.5498A>G NP_001394578.1:p.Tyr1833Cys missense NM_001407652.1:c.5480A>G NP_001394581.1:p.Tyr1827Cys missense NM_001407653.1:c.5480A>G NP_001394582.1:p.Tyr1827Cys missense NM_001407654.1:c.5480A>G NP_001394583.1:p.Tyr1827Cys missense NM_001407655.1:c.5480A>G NP_001394584.1:p.Tyr1827Cys missense NM_001407656.1:c.5477A>G NP_001394585.1:p.Tyr1826Cys missense NM_001407657.1:c.5477A>G NP_001394586.1:p.Tyr1826Cys missense NM_001407658.1:c.5477A>G NP_001394587.1:p.Tyr1826Cys missense NM_001407659.1:c.5474A>G NP_001394588.1:p.Tyr1825Cys missense NM_001407660.1:c.5474A>G NP_001394589.1:p.Tyr1825Cys missense NM_001407661.1:c.5474A>G NP_001394590.1:p.Tyr1825Cys missense NM_001407662.1:c.5474A>G NP_001394591.1:p.Tyr1825Cys missense NM_001407663.1:c.5474A>G NP_001394592.1:p.Tyr1825Cys missense NM_001407664.1:c.5435A>G NP_001394593.1:p.Tyr1812Cys missense NM_001407665.1:c.5435A>G NP_001394594.1:p.Tyr1812Cys missense NM_001407666.1:c.5435A>G NP_001394595.1:p.Tyr1812Cys missense NM_001407667.1:c.5435A>G NP_001394596.1:p.Tyr1812Cys missense NM_001407668.1:c.5435A>G NP_001394597.1:p.Tyr1812Cys missense NM_001407669.1:c.5435A>G NP_001394598.1:p.Tyr1812Cys missense NM_001407670.1:c.5432A>G NP_001394599.1:p.Tyr1811Cys missense NM_001407671.1:c.5432A>G NP_001394600.1:p.Tyr1811Cys missense NM_001407672.1:c.5432A>G NP_001394601.1:p.Tyr1811Cys missense NM_001407673.1:c.5432A>G NP_001394602.1:p.Tyr1811Cys missense NM_001407674.1:c.5432A>G NP_001394603.1:p.Tyr1811Cys missense NM_001407675.1:c.5432A>G NP_001394604.1:p.Tyr1811Cys missense NM_001407676.1:c.5432A>G NP_001394605.1:p.Tyr1811Cys missense NM_001407677.1:c.5432A>G NP_001394606.1:p.Tyr1811Cys missense NM_001407678.1:c.5432A>G NP_001394607.1:p.Tyr1811Cys missense NM_001407679.1:c.5432A>G NP_001394608.1:p.Tyr1811Cys missense NM_001407680.1:c.5432A>G NP_001394609.1:p.Tyr1811Cys missense NM_001407681.1:c.5429A>G NP_001394610.1:p.Tyr1810Cys missense NM_001407682.1:c.5429A>G NP_001394611.1:p.Tyr1810Cys missense NM_001407683.1:c.5429A>G NP_001394612.1:p.Tyr1810Cys missense NM_001407684.1:c.5429A>G NP_001394613.1:p.Tyr1810Cys missense NM_001407685.1:c.5429A>G NP_001394614.1:p.Tyr1810Cys missense NM_001407686.1:c.5429A>G NP_001394615.1:p.Tyr1810Cys missense NM_001407687.1:c.5429A>G NP_001394616.1:p.Tyr1810Cys missense NM_001407688.1:c.5429A>G NP_001394617.1:p.Tyr1810Cys missense NM_001407689.1:c.5429A>G NP_001394618.1:p.Tyr1810Cys missense NM_001407690.1:c.5426A>G NP_001394619.1:p.Tyr1809Cys missense NM_001407691.1:c.5426A>G NP_001394620.1:p.Tyr1809Cys missense NM_001407692.1:c.5417A>G NP_001394621.1:p.Tyr1806Cys missense NM_001407694.1:c.5417A>G NP_001394623.1:p.Tyr1806Cys missense NM_001407695.1:c.5417A>G NP_001394624.1:p.Tyr1806Cys missense NM_001407696.1:c.5417A>G NP_001394625.1:p.Tyr1806Cys missense NM_001407697.1:c.5417A>G NP_001394626.1:p.Tyr1806Cys missense NM_001407698.1:c.5417A>G NP_001394627.1:p.Tyr1806Cys missense NM_001407724.1:c.5417A>G NP_001394653.1:p.Tyr1806Cys missense NM_001407725.1:c.5417A>G NP_001394654.1:p.Tyr1806Cys missense NM_001407726.1:c.5417A>G NP_001394655.1:p.Tyr1806Cys missense NM_001407727.1:c.5417A>G NP_001394656.1:p.Tyr1806Cys missense NM_001407728.1:c.5417A>G NP_001394657.1:p.Tyr1806Cys missense NM_001407729.1:c.5417A>G NP_001394658.1:p.Tyr1806Cys missense NM_001407730.1:c.5417A>G NP_001394659.1:p.Tyr1806Cys missense NM_001407731.1:c.5417A>G NP_001394660.1:p.Tyr1806Cys missense NM_001407732.1:c.5414A>G NP_001394661.1:p.Tyr1805Cys missense NM_001407733.1:c.5414A>G NP_001394662.1:p.Tyr1805Cys missense NM_001407734.1:c.5414A>G NP_001394663.1:p.Tyr1805Cys missense NM_001407735.1:c.5414A>G NP_001394664.1:p.Tyr1805Cys missense NM_001407736.1:c.5414A>G NP_001394665.1:p.Tyr1805Cys missense NM_001407737.1:c.5414A>G NP_001394666.1:p.Tyr1805Cys missense NM_001407738.1:c.5414A>G NP_001394667.1:p.Tyr1805Cys missense NM_001407739.1:c.5414A>G NP_001394668.1:p.Tyr1805Cys missense NM_001407740.1:c.5414A>G NP_001394669.1:p.Tyr1805Cys missense NM_001407741.1:c.5414A>G NP_001394670.1:p.Tyr1805Cys missense NM_001407742.1:c.5414A>G NP_001394671.1:p.Tyr1805Cys missense NM_001407743.1:c.5414A>G NP_001394672.1:p.Tyr1805Cys missense NM_001407744.1:c.5414A>G NP_001394673.1:p.Tyr1805Cys missense NM_001407745.1:c.5414A>G NP_001394674.1:p.Tyr1805Cys missense NM_001407746.1:c.5414A>G NP_001394675.1:p.Tyr1805Cys missense NM_001407747.1:c.5414A>G NP_001394676.1:p.Tyr1805Cys missense NM_001407748.1:c.5414A>G NP_001394677.1:p.Tyr1805Cys missense NM_001407749.1:c.5414A>G NP_001394678.1:p.Tyr1805Cys missense NM_001407750.1:c.5414A>G NP_001394679.1:p.Tyr1805Cys missense NM_001407751.1:c.5414A>G NP_001394680.1:p.Tyr1805Cys missense NM_001407752.1:c.5414A>G NP_001394681.1:p.Tyr1805Cys missense NM_001407838.1:c.5411A>G NP_001394767.1:p.Tyr1804Cys missense NM_001407839.1:c.5411A>G NP_001394768.1:p.Tyr1804Cys missense NM_001407841.1:c.5411A>G NP_001394770.1:p.Tyr1804Cys missense NM_001407842.1:c.5411A>G NP_001394771.1:p.Tyr1804Cys missense NM_001407843.1:c.5411A>G NP_001394772.1:p.Tyr1804Cys missense NM_001407844.1:c.5411A>G NP_001394773.1:p.Tyr1804Cys missense NM_001407845.1:c.5411A>G NP_001394774.1:p.Tyr1804Cys missense NM_001407846.1:c.5411A>G NP_001394775.1:p.Tyr1804Cys missense NM_001407847.1:c.5411A>G NP_001394776.1:p.Tyr1804Cys missense NM_001407848.1:c.5411A>G NP_001394777.1:p.Tyr1804Cys missense NM_001407849.1:c.5411A>G NP_001394778.1:p.Tyr1804Cys missense NM_001407850.1:c.5411A>G NP_001394779.1:p.Tyr1804Cys missense NM_001407851.1:c.5411A>G NP_001394780.1:p.Tyr1804Cys missense NM_001407852.1:c.5411A>G NP_001394781.1:p.Tyr1804Cys missense NM_001407853.1:c.5411A>G NP_001394782.1:p.Tyr1804Cys missense NM_001407854.1:c.*72A>G NM_001407858.1:c.*72A>G NM_001407859.1:c.*72A>G NM_001407860.1:c.*72A>G NM_001407861.1:c.*72A>G NM_001407862.1:c.5357A>G NP_001394791.1:p.Tyr1786Cys missense NM_001407863.1:c.5354A>G NP_001394792.1:p.Tyr1785Cys missense NM_001407874.1:c.5351A>G NP_001394803.1:p.Tyr1784Cys missense NM_001407875.1:c.5351A>G NP_001394804.1:p.Tyr1784Cys missense NM_001407879.1:c.5348A>G NP_001394808.1:p.Tyr1783Cys missense NM_001407881.1:c.5348A>G NP_001394810.1:p.Tyr1783Cys missense NM_001407882.1:c.5348A>G NP_001394811.1:p.Tyr1783Cys missense NM_001407884.1:c.5348A>G NP_001394813.1:p.Tyr1783Cys missense NM_001407885.1:c.5348A>G NP_001394814.1:p.Tyr1783Cys missense NM_001407886.1:c.5348A>G NP_001394815.1:p.Tyr1783Cys missense NM_001407887.1:c.5348A>G NP_001394816.1:p.Tyr1783Cys missense NM_001407889.1:c.5348A>G NP_001394818.1:p.Tyr1783Cys missense NM_001407894.1:c.5345A>G NP_001394823.1:p.Tyr1782Cys missense NM_001407895.1:c.5345A>G NP_001394824.1:p.Tyr1782Cys missense NM_001407896.1:c.5345A>G NP_001394825.1:p.Tyr1782Cys missense NM_001407897.1:c.5345A>G NP_001394826.1:p.Tyr1782Cys missense NM_001407898.1:c.5345A>G NP_001394827.1:p.Tyr1782Cys missense NM_001407899.1:c.5345A>G NP_001394828.1:p.Tyr1782Cys missense NM_001407900.1:c.5345A>G NP_001394829.1:p.Tyr1782Cys missense NM_001407902.1:c.5345A>G NP_001394831.1:p.Tyr1782Cys missense NM_001407904.1:c.5345A>G NP_001394833.1:p.Tyr1782Cys missense NM_001407906.1:c.5345A>G NP_001394835.1:p.Tyr1782Cys missense NM_001407907.1:c.5345A>G NP_001394836.1:p.Tyr1782Cys missense NM_001407908.1:c.5345A>G NP_001394837.1:p.Tyr1782Cys missense NM_001407909.1:c.5345A>G NP_001394838.1:p.Tyr1782Cys missense NM_001407910.1:c.5345A>G NP_001394839.1:p.Tyr1782Cys missense NM_001407915.1:c.5342A>G NP_001394844.1:p.Tyr1781Cys missense NM_001407916.1:c.5342A>G NP_001394845.1:p.Tyr1781Cys missense NM_001407917.1:c.5342A>G NP_001394846.1:p.Tyr1781Cys missense NM_001407918.1:c.5342A>G NP_001394847.1:p.Tyr1781Cys missense NM_001407919.1:c.5306A>G NP_001394848.1:p.Tyr1769Cys missense NM_001407920.1:c.5294A>G NP_001394849.1:p.Tyr1765Cys missense NM_001407921.1:c.5294A>G NP_001394850.1:p.Tyr1765Cys missense NM_001407922.1:c.5294A>G NP_001394851.1:p.Tyr1765Cys missense NM_001407923.1:c.5294A>G NP_001394852.1:p.Tyr1765Cys missense NM_001407924.1:c.5294A>G NP_001394853.1:p.Tyr1765Cys missense NM_001407925.1:c.5294A>G NP_001394854.1:p.Tyr1765Cys missense NM_001407926.1:c.5294A>G NP_001394855.1:p.Tyr1765Cys missense NM_001407927.1:c.5291A>G NP_001394856.1:p.Tyr1764Cys missense NM_001407928.1:c.5291A>G NP_001394857.1:p.Tyr1764Cys missense NM_001407929.1:c.5291A>G NP_001394858.1:p.Tyr1764Cys missense NM_001407930.1:c.5291A>G NP_001394859.1:p.Tyr1764Cys missense NM_001407931.1:c.5291A>G NP_001394860.1:p.Tyr1764Cys missense NM_001407932.1:c.5291A>G NP_001394861.1:p.Tyr1764Cys missense NM_001407933.1:c.5291A>G NP_001394862.1:p.Tyr1764Cys missense NM_001407934.1:c.5288A>G NP_001394863.1:p.Tyr1763Cys missense NM_001407935.1:c.5288A>G NP_001394864.1:p.Tyr1763Cys missense NM_001407936.1:c.5288A>G NP_001394865.1:p.Tyr1763Cys missense NM_001407937.1:c.*72A>G NM_001407938.1:c.*72A>G NM_001407939.1:c.*72A>G NM_001407940.1:c.*72A>G NM_001407941.1:c.*72A>G NM_001407942.1:c.*72A>G NM_001407943.1:c.*72A>G NM_001407944.1:c.*72A>G NM_001407945.1:c.*72A>G NM_001407946.1:c.5225A>G NP_001394875.1:p.Tyr1742Cys missense NM_001407947.1:c.5225A>G NP_001394876.1:p.Tyr1742Cys missense NM_001407948.1:c.5225A>G NP_001394877.1:p.Tyr1742Cys missense NM_001407949.1:c.5225A>G NP_001394878.1:p.Tyr1742Cys missense NM_001407950.1:c.5222A>G NP_001394879.1:p.Tyr1741Cys missense NM_001407951.1:c.5222A>G NP_001394880.1:p.Tyr1741Cys missense NM_001407952.1:c.5222A>G NP_001394881.1:p.Tyr1741Cys missense NM_001407953.1:c.5222A>G NP_001394882.1:p.Tyr1741Cys missense NM_001407954.1:c.5222A>G NP_001394883.1:p.Tyr1741Cys missense NM_001407955.1:c.5222A>G NP_001394884.1:p.Tyr1741Cys missense NM_001407956.1:c.5219A>G NP_001394885.1:p.Tyr1740Cys missense NM_001407957.1:c.5219A>G NP_001394886.1:p.Tyr1740Cys missense NM_001407958.1:c.5219A>G NP_001394887.1:p.Tyr1740Cys missense NM_001407959.1:c.5177A>G NP_001394888.1:p.Tyr1726Cys missense NM_001407960.1:c.5174A>G NP_001394889.1:p.Tyr1725Cys missense NM_001407962.1:c.5174A>G NP_001394891.1:p.Tyr1725Cys missense NM_001407963.1:c.5171A>G NP_001394892.1:p.Tyr1724Cys missense NM_001407964.1:c.5096A>G NP_001394893.1:p.Tyr1699Cys missense NM_001407965.1:c.5051A>G NP_001394894.1:p.Tyr1684Cys missense NM_001407966.1:c.4670A>G NP_001394895.1:p.Tyr1557Cys missense NM_001407967.1:c.4667A>G NP_001394896.1:p.Tyr1556Cys missense NM_001407968.1:c.2954A>G NP_001394897.1:p.Tyr985Cys missense NM_001407969.1:c.2951A>G NP_001394898.1:p.Tyr984Cys missense NM_001407970.1:c.2315A>G NP_001394899.1:p.Tyr772Cys missense NM_001407971.1:c.2315A>G NP_001394900.1:p.Tyr772Cys missense NM_001407972.1:c.2312A>G NP_001394901.1:p.Tyr771Cys missense NM_001407973.1:c.2249A>G NP_001394902.1:p.Tyr750Cys missense NM_001407974.1:c.2249A>G NP_001394903.1:p.Tyr750Cys missense NM_001407975.1:c.2249A>G NP_001394904.1:p.Tyr750Cys missense NM_001407976.1:c.2249A>G NP_001394905.1:p.Tyr750Cys missense NM_001407977.1:c.2249A>G NP_001394906.1:p.Tyr750Cys missense NM_001407978.1:c.2249A>G NP_001394907.1:p.Tyr750Cys missense NM_001407979.1:c.2246A>G NP_001394908.1:p.Tyr749Cys missense NM_001407980.1:c.2246A>G NP_001394909.1:p.Tyr749Cys missense NM_001407981.1:c.2246A>G NP_001394910.1:p.Tyr749Cys missense NM_001407982.1:c.2246A>G NP_001394911.1:p.Tyr749Cys missense NM_001407983.1:c.2246A>G NP_001394912.1:p.Tyr749Cys missense NM_001407984.1:c.2246A>G NP_001394913.1:p.Tyr749Cys missense NM_001407985.1:c.2246A>G NP_001394914.1:p.Tyr749Cys missense NM_001407986.1:c.2246A>G NP_001394915.1:p.Tyr749Cys missense NM_001407990.1:c.2246A>G NP_001394919.1:p.Tyr749Cys missense NM_001407991.1:c.2246A>G NP_001394920.1:p.Tyr749Cys missense NM_001407992.1:c.2246A>G NP_001394921.1:p.Tyr749Cys missense NM_001407993.1:c.2246A>G NP_001394922.1:p.Tyr749Cys missense NM_001408392.1:c.2243A>G NP_001395321.1:p.Tyr748Cys missense NM_001408396.1:c.2243A>G NP_001395325.1:p.Tyr748Cys missense NM_001408397.1:c.2243A>G NP_001395326.1:p.Tyr748Cys missense NM_001408398.1:c.2243A>G NP_001395327.1:p.Tyr748Cys missense NM_001408399.1:c.2243A>G NP_001395328.1:p.Tyr748Cys missense NM_001408400.1:c.2243A>G NP_001395329.1:p.Tyr748Cys missense NM_001408401.1:c.2243A>G NP_001395330.1:p.Tyr748Cys missense NM_001408402.1:c.2243A>G NP_001395331.1:p.Tyr748Cys missense NM_001408403.1:c.2243A>G NP_001395332.1:p.Tyr748Cys missense NM_001408404.1:c.2243A>G NP_001395333.1:p.Tyr748Cys missense NM_001408406.1:c.2240A>G NP_001395335.1:p.Tyr747Cys missense NM_001408407.1:c.2240A>G NP_001395336.1:p.Tyr747Cys missense NM_001408408.1:c.2240A>G NP_001395337.1:p.Tyr747Cys missense NM_001408409.1:c.2237A>G NP_001395338.1:p.Tyr746Cys missense NM_001408410.1:c.2174A>G NP_001395339.1:p.Tyr725Cys missense NM_001408411.1:c.2171A>G NP_001395340.1:p.Tyr724Cys missense NM_001408412.1:c.2168A>G NP_001395341.1:p.Tyr723Cys missense NM_001408413.1:c.2168A>G NP_001395342.1:p.Tyr723Cys missense NM_001408414.1:c.2168A>G NP_001395343.1:p.Tyr723Cys missense NM_001408415.1:c.2168A>G NP_001395344.1:p.Tyr723Cys missense NM_001408416.1:c.2168A>G NP_001395345.1:p.Tyr723Cys missense NM_001408418.1:c.2132A>G NP_001395347.1:p.Tyr711Cys missense NM_001408419.1:c.2132A>G NP_001395348.1:p.Tyr711Cys missense NM_001408420.1:c.2132A>G NP_001395349.1:p.Tyr711Cys missense NM_001408421.1:c.2129A>G NP_001395350.1:p.Tyr710Cys missense NM_001408422.1:c.2129A>G NP_001395351.1:p.Tyr710Cys missense NM_001408423.1:c.2129A>G NP_001395352.1:p.Tyr710Cys missense NM_001408424.1:c.2129A>G NP_001395353.1:p.Tyr710Cys missense NM_001408425.1:c.2126A>G NP_001395354.1:p.Tyr709Cys missense NM_001408426.1:c.2126A>G NP_001395355.1:p.Tyr709Cys missense NM_001408427.1:c.2126A>G NP_001395356.1:p.Tyr709Cys missense NM_001408428.1:c.2126A>G NP_001395357.1:p.Tyr709Cys missense NM_001408429.1:c.2126A>G NP_001395358.1:p.Tyr709Cys missense NM_001408430.1:c.2126A>G NP_001395359.1:p.Tyr709Cys missense NM_001408431.1:c.2126A>G NP_001395360.1:p.Tyr709Cys missense NM_001408432.1:c.2123A>G NP_001395361.1:p.Tyr708Cys missense NM_001408433.1:c.2123A>G NP_001395362.1:p.Tyr708Cys missense NM_001408434.1:c.2123A>G NP_001395363.1:p.Tyr708Cys missense NM_001408435.1:c.2123A>G NP_001395364.1:p.Tyr708Cys missense NM_001408436.1:c.2123A>G NP_001395365.1:p.Tyr708Cys missense NM_001408437.1:c.2123A>G NP_001395366.1:p.Tyr708Cys missense NM_001408438.1:c.2123A>G NP_001395367.1:p.Tyr708Cys missense NM_001408439.1:c.2123A>G NP_001395368.1:p.Tyr708Cys missense NM_001408440.1:c.2123A>G NP_001395369.1:p.Tyr708Cys missense NM_001408441.1:c.2123A>G NP_001395370.1:p.Tyr708Cys missense NM_001408442.1:c.2123A>G NP_001395371.1:p.Tyr708Cys missense NM_001408443.1:c.2123A>G NP_001395372.1:p.Tyr708Cys missense NM_001408444.1:c.2123A>G NP_001395373.1:p.Tyr708Cys missense NM_001408445.1:c.2120A>G NP_001395374.1:p.Tyr707Cys missense NM_001408446.1:c.2120A>G NP_001395375.1:p.Tyr707Cys missense NM_001408447.1:c.2120A>G NP_001395376.1:p.Tyr707Cys missense NM_001408448.1:c.2120A>G NP_001395377.1:p.Tyr707Cys missense NM_001408450.1:c.2120A>G NP_001395379.1:p.Tyr707Cys missense NM_001408451.1:c.2114A>G NP_001395380.1:p.Tyr705Cys missense NM_001408452.1:c.2108A>G NP_001395381.1:p.Tyr703Cys missense NM_001408453.1:c.2108A>G NP_001395382.1:p.Tyr703Cys missense NM_001408454.1:c.2108A>G NP_001395383.1:p.Tyr703Cys missense NM_001408455.1:c.2108A>G NP_001395384.1:p.Tyr703Cys missense NM_001408456.1:c.2108A>G NP_001395385.1:p.Tyr703Cys missense NM_001408457.1:c.2108A>G NP_001395386.1:p.Tyr703Cys missense NM_001408458.1:c.2105A>G NP_001395387.1:p.Tyr702Cys missense NM_001408459.1:c.2105A>G NP_001395388.1:p.Tyr702Cys missense NM_001408460.1:c.2105A>G NP_001395389.1:p.Tyr702Cys missense NM_001408461.1:c.2105A>G NP_001395390.1:p.Tyr702Cys missense NM_001408462.1:c.2105A>G NP_001395391.1:p.Tyr702Cys missense NM_001408463.1:c.2105A>G NP_001395392.1:p.Tyr702Cys missense NM_001408464.1:c.2105A>G NP_001395393.1:p.Tyr702Cys missense NM_001408465.1:c.2105A>G NP_001395394.1:p.Tyr702Cys missense NM_001408466.1:c.2105A>G NP_001395395.1:p.Tyr702Cys missense NM_001408467.1:c.2105A>G NP_001395396.1:p.Tyr702Cys missense NM_001408468.1:c.2102A>G NP_001395397.1:p.Tyr701Cys missense NM_001408469.1:c.2102A>G NP_001395398.1:p.Tyr701Cys missense NM_001408470.1:c.2102A>G NP_001395399.1:p.Tyr701Cys missense NM_001408472.1:c.*72A>G NM_001408473.1:c.*72A>G NM_001408474.1:c.2048A>G NP_001395403.1:p.Tyr683Cys missense NM_001408475.1:c.2045A>G NP_001395404.1:p.Tyr682Cys missense NM_001408476.1:c.2045A>G NP_001395405.1:p.Tyr682Cys missense NM_001408478.1:c.2039A>G NP_001395407.1:p.Tyr680Cys missense NM_001408479.1:c.2039A>G NP_001395408.1:p.Tyr680Cys missense NM_001408480.1:c.2039A>G NP_001395409.1:p.Tyr680Cys missense NM_001408481.1:c.2036A>G NP_001395410.1:p.Tyr679Cys missense NM_001408482.1:c.2036A>G NP_001395411.1:p.Tyr679Cys missense NM_001408483.1:c.2036A>G NP_001395412.1:p.Tyr679Cys missense NM_001408484.1:c.2036A>G NP_001395413.1:p.Tyr679Cys missense NM_001408485.1:c.2036A>G NP_001395414.1:p.Tyr679Cys missense NM_001408489.1:c.2036A>G NP_001395418.1:p.Tyr679Cys missense NM_001408490.1:c.2036A>G NP_001395419.1:p.Tyr679Cys missense NM_001408491.1:c.2036A>G NP_001395420.1:p.Tyr679Cys missense NM_001408492.1:c.2033A>G NP_001395421.1:p.Tyr678Cys missense NM_001408493.1:c.2033A>G NP_001395422.1:p.Tyr678Cys missense NM_001408494.1:c.2009A>G NP_001395423.1:p.Tyr670Cys missense NM_001408495.1:c.2003A>G NP_001395424.1:p.Tyr668Cys missense NM_001408496.1:c.1985A>G NP_001395425.1:p.Tyr662Cys missense NM_001408497.1:c.1985A>G NP_001395426.1:p.Tyr662Cys missense NM_001408498.1:c.1985A>G NP_001395427.1:p.Tyr662Cys missense NM_001408499.1:c.1985A>G NP_001395428.1:p.Tyr662Cys missense NM_001408500.1:c.1985A>G NP_001395429.1:p.Tyr662Cys missense NM_001408501.1:c.1985A>G NP_001395430.1:p.Tyr662Cys missense NM_001408502.1:c.1982A>G NP_001395431.1:p.Tyr661Cys missense NM_001408503.1:c.1982A>G NP_001395432.1:p.Tyr661Cys missense NM_001408504.1:c.1982A>G NP_001395433.1:p.Tyr661Cys missense NM_001408505.1:c.1979A>G NP_001395434.1:p.Tyr660Cys missense NM_001408506.1:c.1922A>G NP_001395435.1:p.Tyr641Cys missense NM_001408507.1:c.1919A>G NP_001395436.1:p.Tyr640Cys missense NM_001408508.1:c.1910A>G NP_001395437.1:p.Tyr637Cys missense NM_001408509.1:c.1907A>G NP_001395438.1:p.Tyr636Cys missense NM_001408510.1:c.1868A>G NP_001395439.1:p.Tyr623Cys missense NM_001408511.1:c.1865A>G NP_001395440.1:p.Tyr622Cys missense NM_001408512.1:c.1745A>G NP_001395441.1:p.Tyr582Cys missense NM_001408513.1:c.1718A>G NP_001395442.1:p.Tyr573Cys missense NM_001408514.1:c.1322A>G NP_001395443.1:p.Tyr441Cys missense NM_007297.4:c.5417A>G NP_009228.2:p.Tyr1806Cys missense NM_007298.4:c.2246A>G NP_009229.2:p.Tyr749Cys missense NM_007299.4:c.*72A>G 3 prime UTR NM_007300.4:c.5621A>G NP_009231.2:p.Tyr1874Cys missense NM_007304.2:c.2246A>G NP_009235.2:p.Tyr749Cys missense NR_027676.2:n.5735A>G non-coding transcript variant NC_000017.11:g.43045712T>C NC_000017.10:g.41197729T>C NG_005905.2:g.172272A>G LRG_292:g.172272A>G LRG_292t1:c.5558A>G LRG_292p1:p.Tyr1853Cys U14680.1:n.5677A>G - Protein change
- Y1853C, Y1806C, Y749C, Y1874C, Y1556C, Y1557C, Y1699C, Y1740C, Y1741C, Y1742C, Y1784C, Y1765C, Y1783C, Y1811C, Y1825C, Y1827C, Y1849C, Y1852C, Y441C, Y636C, Y640C, Y668C, Y670C, Y679C, Y683C, Y709C, Y710C, Y724C, Y746C, Y771C, Y772C, Y1785C, Y1805C, Y1809C, Y1810C, Y1826C, Y1850C, Y573C, Y622C, Y661C, Y680C, Y682C, Y701C, Y703C, Y711C, Y725C, Y748C, Y750C, Y985C, Y1724C, Y1781C, Y1782C, Y1786C, Y1812C, Y1833C, Y1873C, Y1875C, Y582C, Y623C, Y641C, Y660C, Y702C, Y705C, Y747C, Y1684C, Y1725C, Y1726C, Y1763C, Y1764C, Y1769C, Y1804C, Y1834C, Y1848C, Y1851C, Y637C, Y662C, Y678C, Y707C, Y708C, Y723C, Y984C
- Other names
- 5677A>G
- Canonical SPDI
- NC_000017.11:43045711:T:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- functionally_abnormal Sequence Ontology [SO:0002218]
- The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5558A>G, a MISSENSE variant, produced a function score of -2.76, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute, University of Washington]
-
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.
-
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 |
12795 | 14565 |
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. |
---|---|---|---|---|
Conflicting interpretations of pathogenicity (3) |
no assertion criteria provided
|
Mar 2, 2020 | RCV000112703.12 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 16, 2022 | RCV000563885.16 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
May 31, 2022 | RCV000757927.17 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
Mar 21, 2022 | RCV002285262.9 | |
Pathogenic (1) |
no assertion criteria provided
|
Jul 1, 2021 | RCV003162422.8 |
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. |
|
---|---|---|---|---|---|
Likely pathogenic
(May 03, 2018)
|
criteria provided, single submitter
Method: research
|
Hereditary breast and ovarian cancer syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV000886445.1
First in ClinVar: Feb 23, 2019 Last updated: Feb 23, 2019 |
Comment:
The BRCA1 variant designated as p.Y1853C (NM_007294.3:c.5558A>G, historically referred to as 5677A>G) was previously classified as a variant of uncertain significance and is now classified … (more)
The BRCA1 variant designated as p.Y1853C (NM_007294.3:c.5558A>G, historically referred to as 5677A>G) was previously classified as a variant of uncertain significance and is now classified as likely pathogenic. Cosegregation analysis of one observed family was performed using analyze.myvariant.org (Rañola et al, 2018, PMID:28965303). Analysis of this family shows yields a likelihood ratio of 1.9 to 1 (Thompson, et al., 2003, PMID:290079) that this allele is causing cancer within the family. This BRCA1 amino acid position is highly conserved. The variant is not listed in population databases such as ExAC or gnomAD. Functional data suggests that this variant compromises the BRCT domain (Lee 2010, PMID:20516115). More recent functional data is consistent with earlier findings and also indicates that the variant leads to a non-functional protein (Findlay et al, 2018, PMID:30209399). The combined results are consistent with a classification of likely pathogenic. This variant is predicted to alter BRCA1 function and increase breast and ovarian cancer risk. This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study. (less)
Family history: yes
|
|
Pathogenic
(Jun 23, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000665902.4
First in ClinVar: Jan 01, 2018 Last updated: Nov 29, 2022 |
Comment:
The p.Y1853C pathogenic mutation (also known as c.5558A>G), located in coding exon 22 of the BRCA1 gene, results from an A to G substitution at … (more)
The p.Y1853C pathogenic mutation (also known as c.5558A>G), located in coding exon 22 of the BRCA1 gene, results from an A to G substitution at nucleotide position 5558. The tyrosine at codon 1853 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant has been reported in patients with personal and/or family histories of breast and/or ovarian cancer, including many of Japanese and Indian descent (Sugano K et al. Cancer Sci. 2008 Oct;99:1967-76; Kawaku S et al. J. Hum. Genet. 2013 Sep;58:618-21; Nakamura S et al. Breast Cancer. 2015 Sep;22:462-8; Kobayashi Y et al. Jpn J Clin Oncol, 2021 Feb;51:213-217; Tokunaga H et al. PLoS One, 2021 Jan;16:e0236907; Cotrim DP et al. BMC Cancer, 2019 Jan;19:4; Arai M et al. J Hum Genet, 2018 Apr;63:447-457; Singh J et al. Breast Cancer Res Treat, 2018 Jul;170:189-196; Yamaguchi-Kabata Y et al. J Hum Genet, 2018 Feb;63:213-230). This alteration segregates with disease in multiple families (Kawaku S et al. J Hum Genet, 2013 Sep;58:618-21; Parsons MT et al. Hum Mutat, 2019 09;40:1557-1578). This alteration is non-functional in multiple different assays including a haploid cell survival assay, multiple protease/protein stabilization assays, peptide binding and specificity assays and transcription activation assays (Williams RS et al. J. Biol. Chem. 2003 Dec;278:53007-16; Lee MS et al. Cancer Res. 2010 Jun;70:4880-90; Rowling PJ et al. J. Biol. Chem. 2010 Jun;285:20080-7; Findlay GM et al. Nature, 2018 10;562:217-222). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Dec 09, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001576981.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is … (more)
This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1853 of the BRCA1 protein (p.Tyr1853Cys). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 14534301, 20378548, 20516115, 23842040, 30209399). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 55627). This missense change has been observed in individual(s) with hereditary breast and/or ovarian cancer and breast cancer (PMID: 23842040, 29176636, 29470806, 30287823, 30374176). It has also been observed to segregate with disease in related individuals. (less)
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Pathogenic
(May 31, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001362761.2
First in ClinVar: Jun 22, 2020 Last updated: Jul 17, 2022 |
Comment:
Variant summary: BRCA1 c.5558A>G (p.Tyr1853Cys) results in a non-conservative amino acid change located in the BRCT domain (IPR001357) of the encoded protein sequence. Five of … (more)
Variant summary: BRCA1 c.5558A>G (p.Tyr1853Cys) results in a non-conservative amino acid change located in the BRCT domain (IPR001357) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250374 control chromosomes. c.5558A>G has been reported in the literature from Japan, India and Brazil in individuals affected with Hereditary Breast and Ovarian Cancer (examples, Sugano_2008, Nakamura_2015, Kawaku_2013, Arai_2018, Singh_2018, Cotrim_2019, Tsai_2019). These data indicate that the variant is likely to be associated with disease. Several publications report experimental evidence evaluating an impact on protein function (examples, Lee_2010, Kawaku_2013, Woods_2016, Findlay_2018). The most pronounced variant effect results in a reduction of activity across multiple independent measures ranging from transcriptional assays (<10% of WT), structural stability (32% of WT), phosphopeptide binding activity (14% of WT), and protease sensitivity (30% of WT) and loss of homology directed repair (HDR) activity (Findlay_2018). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely pathogenic. Based on the overall directionality of evidence spanning over a decade supporting a pathogenic outcome as evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(Mar 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV002575469.2
First in ClinVar: Oct 01, 2022 Last updated: Mar 04, 2023 |
Comment:
Observed in individuals with a personal and/or family history of breast and/or ovarian cancer (Sugano 2008, Kawaku 2013, Nakamura 2015, Arai 2018, Momozawa 2018, Singh … (more)
Observed in individuals with a personal and/or family history of breast and/or ovarian cancer (Sugano 2008, Kawaku 2013, Nakamura 2015, Arai 2018, Momozawa 2018, Singh 2018, Cotrim 2019, Tsai 2019); Published functional studies demonstrate a damaging effect: impaired protein stability, binding, sensitivity, transciptional activity, and cell survival (Williams 2004, Lee 2010, Rowling 2010, Kawaku 2013, Woods 2016, Findlay 2018, Fernandes 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 5677G>A; This variant is associated with the following publications: (PMID: 15235020, 23842040, 30765603, 20516115, 28781887, 31131967, 20378548, 15133503, 14534301, 30209399, 29470806, 30606148, 30374176, 30287823, 29176636, 24249303, 19016756, 17305420) (less)
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Pathogenic
(Nov 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000908975.4
First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces tyrosine with cysteine at codon 1853 of the BRCA1 protein. Computational prediction tool suggests that this variant may have deleterious impact … (more)
This missense variant replaces tyrosine with cysteine at codon 1853 of the BRCA1 protein. Computational prediction tool suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have reported that this variant impacts BRCA1 function in a haploid cell proliferation assay (PMID: 30209399) and in transcription activation, phosphopeptide binding and protein stability (PMID: 20516115, 23842040). This variant has been reported in at least six individuals affected with breast and/or ovarian cancer (PMID: 19016756, 23842040, 24249303, 30606148, 30287823; Color internal data). This variant has been reported to segregate with breast cancer in at least one family (PMID: 23842040), and a multifactorial analysis has reported segregation and family history likelihood ratios for pathogenicity of 12.663 and 2.2927, respectively (PMID: 31131967). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Uncertain significance
(Jun 20, 2002)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145576.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
Ethnicity/Population group: Western European
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Pathogenic
(Jul 01, 2021)
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no assertion criteria provided
Method: research
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Gastric cancer
Affected status: unknown
Allele origin:
germline
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Laboratory for Genotyping Development, RIKEN
Accession: SCV002758500.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
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Likely pathogenic
(Mar 02, 2020)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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BRCAlab, Lund University
Accession: SCV004243900.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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not provided
(-)
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no classification provided
Method: in vitro
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Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
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Brotman Baty Institute, University of Washington
Accession: SCV001237705.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-2.76343815225029
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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functionally_abnormal
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001237705.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5558A>G, a MISSENSE variant, produced a function score of -2.76, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5558A>G, a MISSENSE variant, produced a function score of -2.76, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. | Usui Y | The New England journal of medicine | 2023 | PMID: 36988593 |
Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes from a dataset of 3,552 Japanese whole genomes (3.5KJPNv2). | Tokunaga H | PloS one | 2021 | PMID: 33428613 |
Retrospective evaluation of risk-reducing salpingo-oophorectomy for BRCA1/2 pathogenic variant carriers among a cohort study in a single institution. | Kobayashi Y | Japanese journal of clinical oncology | 2021 | PMID: 33037428 |
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. | Parsons MT | Human mutation | 2019 | PMID: 31131967 |
Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation. | Fernandes VC | The Journal of biological chemistry | 2019 | PMID: 30765603 |
Prevalence of BRCA1 and BRCA2 pathogenic and likely pathogenic variants in non-selected ovarian carcinoma patients in Brazil. | Cotrim DP | BMC cancer | 2019 | PMID: 30606148 |
Outcomes of 92 patient-driven family studies for reclassification of variants of uncertain significance. | Tsai GJ | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 30374176 |
Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. | Momozawa Y | Nature communications | 2018 | PMID: 30287823 |
Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations. | Singh J | Breast cancer research and treatment | 2018 | PMID: 29470806 |
Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals. | Yamaguchi-Kabata Y | Journal of human genetics | 2018 | PMID: 29192238 |
Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan. | Arai M | Journal of human genetics | 2018 | PMID: 29176636 |
Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance. | Woods NT | NPJ genomic medicine | 2016 | PMID: 28781887 |
Prevalence and differentiation of hereditary breast and ovarian cancers in Japan. | Nakamura S | Breast cancer (Tokyo, Japan) | 2015 | PMID: 24249303 |
Functional analysis of BRCA1 missense variants of uncertain significance in Japanese breast cancer families. | Kawaku S | Journal of human genetics | 2013 | PMID: 23842040 |
Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. | Lee MS | Cancer research | 2010 | PMID: 20516115 |
Toward classification of BRCA1 missense variants using a biophysical approach. | Rowling PJ | The Journal of biological chemistry | 2010 | PMID: 20378548 |
Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer. | Sugano K | Cancer science | 2008 | PMID: 19016756 |
Functional impact of missense variants in BRCA1 predicted by supervised learning. | Karchin R | PLoS computational biology | 2007 | PMID: 17305420 |
Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation. | Abkevich V | Journal of medical genetics | 2004 | PMID: 15235020 |
Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1. | Williams RS | Nature structural & molecular biology | 2004 | PMID: 15133503 |
Detection of protein folding defects caused by BRCA1-BRCT truncation and missense mutations. | Williams RS | The Journal of biological chemistry | 2003 | PMID: 14534301 |
https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
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HelpRecord last updated Apr 20, 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.