ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.476-9dup (rs276174849)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205599 SCV000259239 benign Hereditary breast and ovarian cancer syndrome 2020-11-24 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000113650 SCV000267729 uncertain significance Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
GeneDx RCV000478910 SCV000565790 likely benign not specified 2017-10-13 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 Health, Inc RCV000580196 SCV000683651 likely benign Hereditary cancer-predisposing syndrome 2015-02-23 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000113650 SCV000743241 likely benign Breast-ovarian cancer, familial 2 2015-06-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000478910 SCV000918854 likely benign not specified 2019-05-14 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.476-9dupT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. A functional study reported no impact on splicing, supporting these predictions (Houdayer_2012). The variant allele was found at a frequency of 3.2e-05 in 250658 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.476-9dupT has been reported in the literature in an individual affected with triple-negative breast cancer, but without strong evidence of causality (Wong-Brown_2015). Therefore, this report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. In the UMD database a co-occurrence with another pathogenic variant has been reported (BRCA2 c.4936_4939delGAAA, p.Glu1646GlnfsX23) for this variant, providing supporting evidence for a benign role. Five submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as benign (1x), likely benign (3x) or uncertain significance (1x). Based on the evidence outlined above, the variant was classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001287672 SCV001474383 benign none provided 2020-07-07 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113650 SCV000146942 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000478910 SCV000587552 uncertain significance not specified 2014-02-19 no assertion criteria provided research

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