ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2938G>T (p.Asp980Tyr) (rs397507298)

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 RCV000129246 SCV000184005 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-26 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506200 SCV000600533 uncertain significance not specified 2016-12-05 criteria provided, single submitter clinical testing
GeneDx RCV000766614 SCV000618106 uncertain significance not provided 2017-04-13 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.2938G>T at the cDNA level, p.Asp980Tyr (D980Y) at the protein level, and results in the change of an Aspartic Acid to a Tyrosine (GAT>TAT). Using alternate nomenclature, this variant would be defined as BRCA2 3166G>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Asp980Tyr was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Aspartic Acid and Tyrosine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Asp980Tyr occurs at a position that is not conserved and is not located in a known functional domain. 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 Asp980Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000692326 SCV000820142 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 980 of the BRCA2 protein (p.Asp980Tyr). The aspartic acid residue is weakly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. 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: 37809). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
Sharing Clinical Reports Project (SCRP) RCV000031390 SCV000053995 uncertain significance Breast-ovarian cancer, familial 2 2012-05-16 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.