ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3167A>G (p.Gln1056Arg) (rs431825301)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218077 SCV000275033 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
GeneDx RCV000486491 SCV000570158 uncertain significance not provided 2016-04-29 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.3167A>G at the cDNA level, p.Gln1056Arg (Q1056R) at the protein level, and results in the change of a Glutamine to an Arginine (CAA>CGA). Using alternate nomenclature, this variant would be defined as BRCA2 3395A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Gln1056Arg 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 Glutamine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Gln1056Arg occurs at a position that is not conserved and is located in the RAD51 binding domain (Roy 2012). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA2 Gln1056Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000780000 SCV000916988 uncertain significance not specified 2018-08-27 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3167A>G (p.Gln1056Arg) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.3e-06 in 272980 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.3167A>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000705390 SCV000834384 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-01-22 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 1056 of the BRCA2 protein (p.Gln1056Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs431825301, ExAC 0.02%). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 96785). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly 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.
Sharing Clinical Reports Project (SCRP) RCV000082906 SCV000114980 uncertain significance Breast-ovarian cancer, familial 2 2011-05-12 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.