ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1631C>T (p.Thr544Ile) (rs80358448)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000586961 SCV000071860 likely benign not provided 2019-02-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130669 SCV000185555 likely benign Hereditary cancer-predisposing syndrome 2018-05-23 criteria provided, single submitter clinical testing Other data supporting benign classification;In silico models in agreement (benign)
GeneDx RCV000212211 SCV000210565 likely benign not specified 2017-04-26 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 RCV000083087 SCV000488320 uncertain significance Breast-ovarian cancer, familial 2 2016-02-25 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000212211 SCV000694550 likely benign not specified 2020-01-14 criteria provided, single submitter clinical testing BRCA2 c.1631C>T (p.Thr544Ile) 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 2e-05 in 251030 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1631C>T has been reported in the literature in sequencing studies of individuals affected with variable cohort characteristics, example, nonmucinous ovarian carcinoma (Alsop_2012), prostate cancer (Kote-Jarai_2011), positive family history of pancreatic cancer (Zhen_2015), exome and genome sequencing studies (Zhang_2015). 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 (BRCA1 c.3756_3759delGTCT, p.Ser1253fs*10 in the UMD database; BRCA1 exon13ins6kb in the BIC database; and a non-specified co-occurrence with a reportedly pathogenic variant in the BRCA1/2 gene (Alsop_2012), providing supporting evidence for a benign role. 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. Some have listed overlapping evidences utilized in the context of this evaluation. Five submitters have classified the variant as benign (n=4)/likely benign (n=1) and one as a VUS. Based on the evidence outlined above, the variant was re-classified as likely benign.
Color RCV000130669 SCV000903012 benign Hereditary cancer-predisposing syndrome 2015-11-16 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586961 SCV001133685 likely benign not provided 2019-07-09 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083087 SCV000115161 likely benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000083087 SCV000145901 uncertain significance Breast-ovarian cancer, familial 2 1999-04-12 no assertion criteria provided clinical testing

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