ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8722G>A (p.Val2908Met) (rs483353124)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218173 SCV000273347 uncertain significance Hereditary cancer-predisposing syndrome 2016-01-20 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113989 SCV000147443 uncertain significance Breast-ovarian cancer, familial 2 2012-06-27 no assertion criteria provided clinical testing
GeneDx RCV000482964 SCV000567930 uncertain significance not provided 2018-06-21 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8722G>A at the cDNA level, p.Val2908Met (V2908M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). Using alternate nomenclature, this variant would be defined as BRCA2 8950G>A. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BRCA2 Val2908Met was not observed in large population cohorts (Lek 2016). This variant is located in the DNA binding domain (Yang 2002). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Val2908Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000821493 SCV000962251 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-02 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 2908 of the BRCA2 protein (p.Val2908Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. 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: 126188). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.