ClinVar Miner

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

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breast Cancer Information Core (BIC) (BRCA2) RCV000113650 SCV000146942 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000580196 SCV000683651 likely benign Hereditary cancer-predisposing syndrome 2015-02-23 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.
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
Integrated Genetics/Laboratory Corporation of America RCV000478910 SCV000918854 likely benign not specified 2018-03-12 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.476-9dupT is located at a position not widely known to affect splicing. Five out of five computational tools predict no significant impact on normal splicing. A functional study, Houdayer_2012, supports these predictions with no observed impact on splicing.The variant was observed with an allele frequency of 3.3e-05 in 276606 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (3.3e-05 vs 0.00075), allowing no conclusion about variant significance. A publication, Wong-Brown_2015, cites the variant in an affected individual, however, with limited information (ie, lack of co-occurrence and cosegregation data). A co-occurrence with another pathogenic variant(s) have been reported (BRCA2 c.4936_4939delGAAA/p.Glu1646GlnfsX23, scored pathogenic by internal classification system), providing supporting evidence for a benign role. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign/benign." Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000205599 SCV000259239 benign Hereditary breast and ovarian cancer syndrome 2017-10-18 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
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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