ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.10154G>A (p.Arg3385His) (rs80358398)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162743 SCV000213215 benign Hereditary cancer-predisposing syndrome 2015-06-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000031303 SCV000145761 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768613 SCV000324844 likely benign Breast and/or ovarian cancer 2015-09-11 criteria provided, single submitter clinical testing
Color RCV000162743 SCV000910750 benign Hereditary cancer-predisposing syndrome 2016-04-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000374528 SCV000592314 likely benign not specified criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725588 SCV000337948 uncertain significance not provided 2015-11-24 criteria provided, single submitter clinical testing
GeneDx RCV000374528 SCV000512405 likely benign not specified 2015-12-28 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.
Integrated Genetics/Laboratory Corporation of America RCV000374528 SCV000916866 uncertain significance not specified 2018-12-12 criteria provided, single submitter clinical testing Variant summary: The variant, BRCA2 c.10154G>A (p.Arg3385His) 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 1.6e-05 in 246046 control chromosomes (gnomAD and Juwle_2012). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant c.10154G>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer or stomach adenocarcinoma (Juwle _2012, Kote-Jarai _2011, Laitman _2011, Lu_2015). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant have been reported (BRCA2 c.7558C>T, p.Arg2520X), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (5 X benign/likely benign and 1X VUS). Based on the evidence outlined above, the variant was classified as VUS- possibly benign.
Invitae RCV000043722 SCV000071735 likely benign Hereditary breast and ovarian cancer syndrome 2017-11-03 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031303 SCV000053908 benign Breast-ovarian cancer, familial 2 2012-03-29 no assertion criteria provided clinical testing
True Health Diagnostics RCV000162743 SCV000787915 likely benign Hereditary cancer-predisposing syndrome 2017-09-29 no assertion criteria provided clinical testing

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