ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.811G>A (p.Gly271Arg) (rs786204274)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218275 SCV000274810 likely benign Hereditary cancer-predisposing syndrome 2015-03-23 criteria provided, single submitter clinical testing
Color RCV000218275 SCV000910942 likely benign Hereditary cancer-predisposing syndrome 2016-08-18 criteria provided, single submitter clinical testing
GeneDx RCV000657096 SCV000617910 uncertain significance not provided 2017-09-06 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.811G>A at the cDNA level, p.Gly271Arg (G271R) at the protein level, and results in the change of a Glycine to an Arginine (GGG>AGG). Using alternate nomenclature, this variant would be defined as BRCA2 1039G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Gly271Arg was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Glycine and Arginine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Gly271Arg occurs at a position that is not conserved and is not located in a known functional domain. 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 Gly271Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000560451 SCV000635641 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-26 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 271 of the BRCA2 protein (p.Gly271Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. 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: 188426). 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 arginine 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.
Mendelics RCV000560451 SCV000838748 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507723 SCV000600787 uncertain significance not specified 2017-04-08 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.