ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9583A>G (p.Thr3195Ala) (rs80359227)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045861 SCV000073874 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129471 SCV000184241 likely benign Hereditary cancer-predisposing syndrome 2018-09-07 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000083162 SCV000296504 uncertain significance Breast-ovarian cancer, familial 2 2016-06-07 criteria provided, single submitter clinical testing
Counsyl RCV000083162 SCV000487986 uncertain significance Breast-ovarian cancer, familial 2 2015-12-10 criteria provided, single submitter clinical testing
GeneDx RCV000427171 SCV000532127 likely benign not specified 2018-02-27 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 RCV000427171 SCV000695253 uncertain significance not specified 2019-09-07 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.9583A>G (p.Thr3195Ala) results in a non-conservative amino acid change in 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 1.2e-05 in 251412 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.9583A>G has been reported in the literature in one family with high risk of breast or ovarian cancer (Simard_2007). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six 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 (benign/likely benign, n=3; uncertain significance, n=3). Based on the evidence outlined above, the variant was classified as uncertain significance.
Color RCV000129471 SCV000911111 benign Hereditary cancer-predisposing syndrome 2017-01-09 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000427171 SCV001158035 uncertain significance not specified 2018-11-29 criteria provided, single submitter clinical testing The BRCA2 c.9583A>G; p.Thr3195Ala variant (rs80359227), is reported in the literature in at least one individual with a family history of breast and/or ovarian cancer (Simard 2007). This variant is reported as uncertain significance/likely benign by multiple laboratories in ClinVar (Variation ID: 52872), and is only observed on three alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The threonine at codon 3195 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Thr3195Ala variant is uncertain at this time. References: Simard J et al. Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer. J Med Genet. 2007 Feb;44(2):107-21.
Sharing Clinical Reports Project (SCRP) RCV000083162 SCV000115236 likely benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000083162 SCV000147669 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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