ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2443A>G (p.Met815Val) (rs786203814)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167284 SCV000218127 uncertain significance Hereditary cancer-predisposing syndrome 2015-08-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Counsyl RCV000410955 SCV000488082 uncertain significance Breast-ovarian cancer, familial 2 2015-12-22 criteria provided, single submitter clinical testing
Invitae RCV000456518 SCV000549785 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-12 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 815 of the BRCA2 protein (p.Met815Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (rs786203814, ExAC no frequency). This variant has not been reported in the literature in individuals with a BRCA2-related disease. It has been reported in an individual in the Leiden Open-source Variation Database, and occurs with a pathogenic variant in BRCA2 in that individual (PMID: 21520333). While it is unknown if these variants are on the same or opposite chromosomes, this observation suggests that the c.2443A>G variant is not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 187546). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The valine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional 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.
Color RCV000167284 SCV000903137 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-24 criteria provided, single submitter clinical testing

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