ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8092G>A (p.Ala2698Thr) (rs80359052)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000074554 SCV000108639 likely benign not specified 2017-11-03 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.
Ambry Genetics RCV000129982 SCV000184806 likely benign Hereditary cancer-predisposing syndrome 2018-04-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other strong data supporting benign classification
Counsyl RCV000031720 SCV000487854 uncertain significance Breast-ovarian cancer, familial 2 2015-11-23 criteria provided, single submitter clinical testing
Invitae RCV000755863 SCV000635637 likely benign not provided 2019-03-01 criteria provided, single submitter clinical testing
Mendelics RCV000531554 SCV000838867 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755863 SCV000883489 uncertain significance not provided 2017-07-19 criteria provided, single submitter clinical testing The BRCA2 c.8092G>A;p.Ala2698Thr variant has been described in the medical literature in an individual with breast cancer and a family history of cancer (Manguoglu 2010). The variant is listed in the ClinVar database (Variation ID: 38138), the dbSNP variant database (rs80359052), and the Genome Aggregation Database with an allele frequency of 0.004331 percent (12/277058 alleles). The amino acid at this position is weakly conserved across species, with several mammalian species with threonine at this position, and computational algorithms (AlignGVGD, SIFT, MutationTaster) predict this variant is tolerated. Considering available information, the clinical significance cannot be determined with certainty. References: Manguoglu E et al. Germline mutations of BRCA1 and BRCA2 genes in Turkish breast, ovarian, and prostate cancer patients. Cancer Genet Cytogenet. 2010 Dec;203(2):230-7.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000755863 SCV000889152 uncertain significance not provided 2018-12-24 criteria provided, single submitter clinical testing
Color RCV000129982 SCV000905495 likely benign Hereditary cancer-predisposing syndrome 2015-09-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000074554 SCV000918820 uncertain significance not specified 2019-04-18 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.8092G>A (p.Ala2698Thr) results in a non-conservative amino acid change located in the BRCA2, OB1 domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 251318 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.8092G>A has been reported in the literature in individuals affected with Breast and Ovarian Cancer as well as other cancer types (Dong_2018, Kandoth_2013, Lu_2015, Manguoglu_2010, Pal_2015, Wagner_1999). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variant(s) have been reported (BRCA2 c.1321_1324delACTT, p.Thr441GlnfsX18, internal data), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (5 VUS, 2 Likely benign). Based on the evidence outlined above, the variant was classified as a VUS - possibly benign variant.
Mendelics RCV000031720 SCV001139205 uncertain significance Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031720 SCV000054327 uncertain significance Breast-ovarian cancer, familial 2 2007-03-13 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031720 SCV000147272 uncertain significance Breast-ovarian cancer, familial 2 1998-11-30 no assertion criteria provided clinical testing

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