ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.10240A>G (p.Thr3414Ala) (rs80358405)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129127 SCV000183845 likely benign Hereditary cancer-predisposing syndrome 2018-05-18 criteria provided, single submitter clinical testing Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
GeneDx RCV000160262 SCV000210701 likely benign not specified 2017-09-20 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.
Counsyl RCV000077652 SCV000489448 uncertain significance Breast-ovarian cancer, familial 2 2016-10-11 criteria provided, single submitter clinical testing
Invitae RCV000458506 SCV000549766 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-03 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129127 SCV000903280 benign Hereditary cancer-predisposing syndrome 2017-06-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000160262 SCV000916836 uncertain significance not specified 2018-02-05 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.10240A>G (p.Thr3414Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.9e-05 in 276468 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (2.9e-05 vs 0.00075), allowing no conclusion about variant significance. c.10240A>G has been reported in the literature in affected individuals. These report(s) do 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. Multiple clinical diagnostic laboratories/databases have classified this variant as VUS, and two labs/databases classified it as Likely benign, all without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985459 SCV001133668 likely benign not provided 2019-08-19 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000160262 SCV001159916 uncertain significance not specified 2018-08-27 criteria provided, single submitter clinical testing The BRCA2 c.10240A>G; p.Thr3414Alavariant (rs80358405) is reported in the literature in two families with a history of breast and ovarian cancer (Riahi 2015). This variant is reported in ClinVar (Variation ID: 91744) and is found in the non-Finnish European population with an overall allele frequency of 0.006% (8/126308 alleles) in the Genome Aggregation Database. The threonine at codon 3414 is weakly conserved, and computational analyses (SIFT: tolerated, PolyPhen-2: damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Thr3414Ala variant is uncertain at this time. References: Riahi A et al. Mutation spectrum and prevalence of BRCA1 and BRCA2 genes in patients with familial and early-onset breast/ovarian cancer from Tunisia. Clin Genet. 2015 Feb;87(2):155-60.
Sharing Clinical Reports Project (SCRP) RCV000077652 SCV000109455 likely benign Breast-ovarian cancer, familial 2 2007-07-09 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077652 SCV000145771 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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