ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2083G>T (p.Asp695Tyr) (rs28897681)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000047706 SCV000075719 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV000166737 SCV000217548 likely benign Hereditary cancer-predisposing syndrome 2017-12-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting benign classification
GeneDx RCV000430793 SCV000512291 likely benign not specified 2017-03-20 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000430793 SCV000591369 likely benign not specified 2014-01-28 criteria provided, single submitter clinical testing
Color RCV000166737 SCV000903863 likely benign Hereditary cancer-predisposing syndrome 2016-03-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000430793 SCV000918729 likely benign not specified 2018-04-16 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.2083G>T (p.Asp695Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.7e-05 in 276880 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (4.7e-05 vs 1.00e-03), allowing no conclusion about variant significance. This variant, c.2083G>T, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Lu_2012, Anczukow_2008). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant(s) have been reported (BRCA1: c.5266dup (p.Gln1756ProfsX74) and c.3760A (p.Lys1254X); BRCA2: c.145G>T (p.Glu49X), c.5350_5351delAA (p.Asn1784HisfsX2), and c.1800T>G (p.Tyr600X)), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified this variant as likely benign (2x) and VUS (1x). Based on the evidence outlined above, the variant was classified as likely benign.
Sharing Clinical Reports Project (SCRP) RCV000083177 SCV000115251 benign Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083177 SCV000144296 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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