ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8697A>G (p.Gln2899=) (rs786203707)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167127 SCV000217957 likely benign Hereditary cancer-predisposing syndrome 2015-05-01 criteria provided, single submitter clinical testing
Color RCV000167127 SCV000689146 likely benign Hereditary cancer-predisposing syndrome 2017-04-17 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495249 SCV000578739 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/).
GeneDx RCV000429155 SCV000523231 likely benign not specified 2016-01-08 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.
Integrated Genetics/Laboratory Corporation of America RCV000429155 SCV000918941 uncertain significance not specified 2018-06-29 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.8697A>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. 4/5 predict creation/strengthening of a cryptic splicing acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 246140 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.8697A>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (4 likely benign and 1 VUS). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Invitae RCV000472816 SCV000549731 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-19 criteria provided, single submitter clinical testing This sequence change affects codon 2899 of the BRCA2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the BRCA2 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 187403). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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