ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9275A>G (p.Tyr3092Cys) (rs80359195)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000424310 SCV000602842 likely benign not specified 2017-02-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131684 SCV000186720 likely benign Hereditary cancer-predisposing syndrome 2017-09-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting benign classification,Other data supporting benign classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000077466 SCV000147597 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000131684 SCV000684046 likely benign Hereditary cancer-predisposing syndrome 2016-09-16 criteria provided, single submitter clinical testing
Counsyl RCV000077466 SCV000221030 likely benign Breast-ovarian cancer, familial 2 2015-01-15 criteria provided, single submitter literature only
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077466 SCV000744561 uncertain significance Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000424310 SCV000592272 uncertain significance not specified 2015-10-09 criteria provided, single submitter clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735623 SCV000863761 likely benign Breast and/or ovarian cancer 2010-04-21 no assertion criteria provided clinical testing
GeneDx RCV000424310 SCV000512396 likely benign not specified 2017-08-21 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.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000077466 SCV000743363 uncertain significance Breast-ovarian cancer, familial 2 2014-10-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586462 SCV000695231 likely benign not provided 2017-04-07 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9275A>G (p.Tyr3092Cys) variant involves the alteration of a conserved nucleotide, resulting in a missense substitution. The variant lies within the BRCA2, oligonucleotide/oligosaccharide-binding 3 domain and the nucleic acid-binding, OB-fold domain (InterPro), and 4/4 in silico tools predict a damaging outcome for this variant. This variant was found in the large control database ExAC, as well as publications, at a frequency of 0.0000695 (8/115184 control chromosomes). However, in ExAC it was predominantly observed in the Latino subpopulation at a frequency of 0.000451 (5/11088 control Latino chromosomes). This frequency is slightly less than the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), suggesting this could potentially be a benign polymorphism found primarily in the populations of Latino origin. This variant has been reported in affected individuals without strong evidence for causality. Functional studies show that the variant does not affect splicing (Caux-Moncoutier_2009, Houdayer_2012) and has comparable to wild type function for homology-directed repair activity (Guidugli_2013). UMD reports the variant to co-occur with a pathogneic BRCA2 variant, c.6275_6276delTT (p.Leu2092ProfsX7), supporting a non-pathogenic role for the variant of interest. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as likely benign.
Invitae RCV000045774 SCV000073787 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-27 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077466 SCV000109264 likely benign Breast-ovarian cancer, familial 2 2012-06-14 no assertion criteria provided clinical testing
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000077466 SCV000267234 uncertain significance Breast-ovarian cancer, familial 2 2016-03-18 criteria provided, single submitter reference population

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