ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8036A>G (p.Asp2679Gly) (rs80359041)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131797 SCV000186848 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000113859 SCV000147255 uncertain significance Breast-ovarian cancer, familial 2 2001-10-29 no assertion criteria provided clinical testing
Color RCV000131797 SCV000683938 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-11 criteria provided, single submitter clinical testing
Counsyl RCV000113859 SCV000489186 uncertain significance Breast-ovarian cancer, familial 2 2016-08-31 criteria provided, single submitter clinical testing
GeneDx RCV000484310 SCV000567541 likely benign not specified 2018-02-22 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 RCV000484310 SCV000916951 uncertain significance not specified 2018-07-24 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.8036A>G (p.Asp2679Gly) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function, in addition in silico studies also predicted that the variant probably impairs protein function (Karchin_2008, Doss_2014). The variant allele was found at a frequency of 2.5e-05 in 276984 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.8036A>G has been reported in the literature in individuals with risk of Hereditary Breast and Ovarian Cancer (Guidugli_2012). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. At least two publications report experimental evidence evaluating an impact on protein function. These results showed neutral effect of this variant (Guidugli_2012; Hart-Couch_2018). Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (5 VUS, 1 likely benign). Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000045397 SCV000073410 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-06-24 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 2679 of the BRCA2 protein (p.Asp2679Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs80359041, ExAC 0.009%). This variant has been reported in individuals in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 52481). Experimental studies have shown that this missense change does not alter the DNA repair activity of BRCA2 (PMID: 23108138). General algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD), and an algorithm developed specifically for the BRCA2 gene (PMID: 19043619), suggest that this missense change is likely to be disruptive. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000484310 SCV000600779 uncertain significance not specified 2017-04-10 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759667 SCV000889149 uncertain significance not provided 2017-12-02 criteria provided, single submitter 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.