ClinVar Miner

Submissions for variant NM_000059.4(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
Invitae RCV001086927 SCV000071735 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162743 SCV000213215 benign Hereditary cancer-predisposing syndrome 2015-06-23 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
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
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.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000374528 SCV000592314 likely benign not specified criteria provided, single submitter clinical testing
Color RCV000162743 SCV000910750 benign Hereditary cancer-predisposing syndrome 2016-04-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000374528 SCV000916866 likely benign not specified 2019-12-23 criteria provided, single submitter clinical testing Variant summary: 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 251270 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.10154G>A has been reported in the literature in sequencing studies of individuals affected with Hereditary Breast and Ovarian Cancer or stomach adenocarcinoma (Juwle _2012, Kote-Jarai _2011, Laitman _2011, Lu_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. At-least one co-occurrence with another pathogenic variant has been reported (BRCA2 c.7558C>T, p.Arg2520X, UMD database), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (benign, n=2, likely benign, n=4, and VUS, n=1). We have tracked this variant for six years at our laboratory (2014-2019) and have previously classified this variant as a VUS-possibly benign mainly due to its rarity. However, no convincing evidence supporting a pathogenic outcome has emerged in this time frame and the majority consensus in the field seems to be shifting to a benign outcome. Based on the evidence outlined above, the variant was re-classified as likely benign.
Sharing Clinical Reports Project (SCRP) RCV000031303 SCV000053908 benign Breast-ovarian cancer, familial 2 2012-03-29 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031303 SCV000145761 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 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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