ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8356G>A (p.Ala2786Thr) (rs80359077)

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
3DMed Clinical Laboratory Inc RCV000677863 SCV000804024 uncertain significance Malignant tumor of prostate 2017-07-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130784 SCV000185677 uncertain significance Hereditary cancer-predisposing syndrome 2017-07-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000077436 SCV000147331 uncertain significance Breast-ovarian cancer, familial 2 2010-09-18 no assertion criteria provided clinical testing
Color RCV000130784 SCV000683960 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-04 criteria provided, single submitter clinical testing
Counsyl RCV000077436 SCV000786060 uncertain significance Breast-ovarian cancer, familial 2 2018-02-15 criteria provided, single submitter clinical testing
GeneDx RCV000220216 SCV000278880 likely benign not specified 2017-12-06 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 RCV000588037 SCV000695146 uncertain significance not provided 2016-10-21 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.8356G>A (p.Ala2786Thr) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. This variant was found in 8/122244 control chromosomes (1 homozygote), predominantly observed in the East Asian subpopulation at a frequency of 0.0008092 (7/8650). This frequency is about the same frequency as the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), suggesting it may be a benign polymorphism found primarily in the populations of East Asian origin. The variant of interest has been reported in the literature in affected individuals of Chinese origin, without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS until additional clinical and functional evidence become available.
Invitae RCV000045489 SCV000073502 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-01-30 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 2786 of the BRCA2 protein (p.Ala2786Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs80359077, ExAC 0.08%). This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 18627636, 14973102, 27376475, 26221963, 26689913, 28222693, Invitae). However, in one of these individuals a pathogenic allele was also identified in BRCA1, which suggests that this c.8356G>A variant was not the primary cause of disease. This variant is also known as 8584G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 52560). 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: "Deleterious"; PolyPhen-2: "Probably 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) RCV000077436 SCV000109234 likely benign Breast-ovarian cancer, familial 2 2012-06-19 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.