ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4718G>A (p.Cys1573Tyr) (rs56249050)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001081098 SCV000072489 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000132250 SCV000187333 likely benign Hereditary cancer-predisposing syndrome 2018-11-14 criteria provided, single submitter clinical testing Other data supporting benign classification;In silico models in agreement (benign)
GeneDx RCV000445221 SCV000518764 likely benign not specified 2016-06-14 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.
Color RCV000132250 SCV000683648 likely benign Hereditary cancer-predisposing syndrome 2015-03-11 criteria provided, single submitter clinical testing
Counsyl RCV000077337 SCV000786380 uncertain significance Breast-ovarian cancer, familial 2 2018-04-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758898 SCV000887823 likely benign not provided 2018-03-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000445221 SCV000918863 uncertain significance not specified 2019-11-08 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.4718G>A (p.Cys1573Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251100 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4718G>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Spitzer_2000, Tutt_2010, He_2016). A co-occurrence with another pathogenic BRCA1 variant, c.1687C>T (p.Q563X) has been reported, providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submissions (evaluation after 2014) cites the variant 5 times as likely benign and once as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Sharing Clinical Reports Project (SCRP) RCV000077337 SCV000109134 benign Breast-ovarian cancer, familial 2 2012-03-12 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077337 SCV000146474 uncertain significance Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing

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