ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8215G>A (p.Val2739Ile) (rs80359069)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080912 SCV000073466 benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129733 SCV000184538 likely benign Hereditary cancer-predisposing syndrome 2018-10-05 criteria provided, single submitter clinical testing Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene;In silico models in agreement (benign)
GeneDx RCV000214196 SCV000278879 likely benign not specified 2018-02-22 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 RCV000214196 SCV000494391 likely benign not specified 2019-08-13 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.8215G>A (p.Val2739Ile) results in a conservative amino acid change located in the OB1 domain (IPR015187) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 249656 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.8215G>A, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer without strong evidence for pathogenicity (Carney_2010, Trujillano_2015, Wong-Brown_2015, Tung_2015). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variants have been reported (BRCA2 c.6486_6489delACAA , p.Lys2162fsX5; BRCA1 c.81-2delA), providing supporting evidence for a benign role. In a functional assay (Karchin_2008), this variant retained approximately 70% of homology-directed repair (HDR) activity (compared to wild-type). Eight other submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories have classified the variant as VUS (2x), Likely benign (5x) and Benign (1X). Based on the evidence outlined above, the variant was classified as likely benign.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000214196 SCV000592179 uncertain significance not specified 2016-03-23 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000045453 SCV000600791 likely benign not provided 2018-08-16 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077431 SCV000744538 likely benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Counsyl RCV000077431 SCV000785552 uncertain significance Breast-ovarian cancer, familial 2 2017-09-08 criteria provided, single submitter clinical testing
Color RCV000129733 SCV000902886 likely benign Hereditary cancer-predisposing syndrome 2015-07-23 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001110061 SCV001267449 uncertain significance Fanconi anemia, complementation group D1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000077431 SCV001267450 uncertain significance Breast-ovarian cancer, familial 2 2017-12-19 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Sharing Clinical Reports Project (SCRP) RCV000077431 SCV000109229 uncertain significance Breast-ovarian cancer, familial 2 2012-01-13 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077431 SCV000147300 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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