ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6841+11A>G (rs730881592)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160237 SCV000210637 benign not specified 2014-09-08 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.
Invitae RCV000196508 SCV000253029 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-20 criteria provided, single submitter clinical testing
Color Health, Inc RCV000580252 SCV000683817 likely benign Hereditary cancer-predisposing syndrome 2016-11-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000160237 SCV001362776 likely benign not specified 2020-10-12 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6841+11A>G 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. 4/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.4e-05 in 250020 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer Syndrome (4.4e-05 vs 0.00075), allowing no conclusion about variant significance. c.6841+11A>G has been reported in the literature in at least an individual affected with breast cancer (Borg_2012). This report however, does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer Syndrome. Co-occurrence with another pathogenic variant has been reported (BRCA1 c.5154G>A, p.Trp1718X; UMD database), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two other ClinVar submitters (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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