ClinVar Miner

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

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001082678 SCV000073502 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130784 SCV000185677 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-15 criteria provided, single submitter clinical testing The p.A2786T variant (also known as c.8356G>A), located in coding exon 18 of the BRCA2 gene, results from a G to A substitution at nucleotide position 8356. The alanine at codon 2786 is replaced by threonine, an amino acid with similar properties. This variant has been reported in several studies of Chinese women with breast cancer (Suter NM et al. Cancer Epidemiol. Biomarkers Prev. 2004 Feb; 13(2):181-9; Thirthagiri E et al. Breast Cancer Res. 2008; 10(4):R59; Wong ES et al. PLoS ONE. 2015;10(7):e0134408). In a case-control study of Chinese, Malay, and Indian individuals, it was observed in 8/2088 breast cancer cases and 4/1448 healthy controls (Lai KN. BMC Cancer. 2017 Feb;17(1):149). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
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.
Color Health, Inc RCV000130784 SCV000683960 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-10 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 2786 of the BRCA2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 14973102, 18627636, 26221963, 28222693). It has also been reported in unaffected individuals (PMID: 27157322, 28222693). This variant has been identified in 16/282820 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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.
Counsyl RCV000077436 SCV000786060 uncertain significance Breast-ovarian cancer, familial 2 2018-02-15 criteria provided, single submitter clinical testing
3DMed Clinical Laboratory Inc RCV000677863 SCV000804024 uncertain significance Malignant tumor of prostate 2017-07-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588037 SCV001133932 uncertain significance not provided 2020-07-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286197 SCV001472729 uncertain significance none provided 2019-11-11 criteria provided, single submitter clinical testing The BRCA2 c.8356G>A; p.Ala2786Thr variant (rs80359077), also known as 8584G>A for traditional nomenclature, is reported in the literature in individuals with hereditary breast and ovarian cancer syndrome (Lai 2017, Suter 2004, Thirthagiri 2008, Wong 2015), but is also reported in healthy controls (Lai 2017). This variant is reported in ClinVar (Variation ID: 52560). It is found in the general East Asian population with an allele frequency of 0.08% (15/19954 alleles, including 1 homozygote) in the Genome Aggregation Database. The alanine at codon 2786 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of this variant is uncertain at this time. REFERENCES Lai KN et al. Characterization of BRCA1 and BRCA2 variants in multi-ethnic Asian cohort from a Malaysian case-control study. BMC Cancer. 2017 Feb 22;17(1):149. Suter NM et al. BRCA1 and BRCA2 mutations in women from Shanghai China. Cancer Epidemiol Biomarkers Prev. 2004 Feb;13(2):181-9. Thirthagiri E et al. Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer. Breast Cancer Res. 2008;10(4):R59. Wong ES et al. Predictive Factors for BRCA1 and BRCA2 Genetic Testing in an Asian Clinic-Based Population. PLoS One. 2015 Jul 29;10(7):e0134408.
Sharing Clinical Reports Project (SCRP) RCV000077436 SCV000109234 likely benign Breast-ovarian cancer, familial 2 2012-06-19 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077436 SCV000147331 uncertain significance Breast-ovarian cancer, familial 2 2010-09-18 no assertion criteria provided clinical testing

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