ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9234C>T (p.Val3078=) (rs587782428)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495698 SCV000578815 likely benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Ambry Genetics RCV000131482 SCV000186469 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000590584 SCV000259605 likely benign not provided 2019-02-11 criteria provided, single submitter clinical testing
Color RCV000131482 SCV000684038 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000608709 SCV000695219 likely benign not specified 2018-04-27 criteria provided, single submitter clinical testing BRCA2 c.9234C>T alters a non-conserved nucleotide resulting in a synonymous change. 4/4 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 1.6e-05 in 250876 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.9234C>T has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer in whom co-occurrences with other pathogenic variant(s) have been reported (BRCA1 c.4165_4166delAG, p.Ser1389Terfs), providing supporting evidence for a benign role (Sanz_2010). At least one publication reports experimental evidence evaluating an impact on splicing reporting a partial skipping of exon 24, however, does not allow convincing conclusions about the variant effect as the primary data was not included (Sanz_2010). Seven submitters including one expert panel (ENIGMA) have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple submitters reported the variant with conflicting assessments while the expert panel classifies the variant a likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx RCV000608709 SCV000730936 benign not specified 2015-09-14 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.
Counsyl RCV000495698 SCV000785176 uncertain significance Breast-ovarian cancer, familial 2 2017-05-26 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590584 SCV000889177 likely benign not provided 2018-04-25 criteria provided, single submitter clinical testing

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