ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5527G>C (p.Ala1843Pro) (rs80357019)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570342 SCV000665866 likely pathogenic Hereditary cancer-predisposing syndrome 2016-09-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Breast Cancer Information Core (BIC) (BRCA1) RCV000112695 SCV000145567 uncertain significance Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781015 SCV000918767 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-13 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5527G>C (p.Ala1843Pro) results in a non-conservative amino acid change located in the BRCT domain 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 246124 control chromosomes (gnomAD). c.5527G>C has been reported in the literature in an individual affected with Hereditary Breast and Ovarian Cancer (Sekine_2001). This data does not allow any conclusion about variant significance. Several functional studies have found the variant to be moderately destabilizing in multiple measures such as reduced protein stability, significantly decreased transcriptional activity, and homologous recombination (Lee_2010, Rowling_2010, Gaboriau_2015). A ClinVar submission from another clinical diagnostic laboratory (evaluation after 2014) cites the variant as "likely pathogenic." Based on the evidence outlined above, the variant was classified as likely pathogenic.

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