ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8323A>G (p.Met2775Val) (rs767209209)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482965 SCV000572461 uncertain significance not provided 2016-12-12 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8323A>G at the cDNA level, p.Met2775Val (M2775V) at the protein level, and results in the change of a Methionine to a Valine (ATG>GTG). Using alternate nomenclature, this variant would be defined as BRCA2 8551A>G. This variant has been observed in at least one individual with a family history of breast or ovarian cancer (Jarhelle 2016). BRCA2 Met2775Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Methionine and Valine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Met2775Val occurs at a position that is not conserved and is located in the DNA binding domain (Yang 2002). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Met2775Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000532115 SCV000635658 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-05-06 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 2775 of the BRCA2 protein (p.Met2775Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs767209209, ExAC 0.002%). This variant has been observed in an individual affected with breast or ovarian cancer (PMID: 27495310). ClinVar contains an entry for this variant (Variation ID: 254645). 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 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 and their clinical significance is uncertain. 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.
Department of Medical Genetics,University Hospital of North Norway RCV000241308 SCV000301454 uncertain significance Breast-ovarian cancer, familial 2 2016-05-01 no assertion criteria provided clinical testing

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.