ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5921C>T (p.Thr1974Ile) (rs55730620)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166046 SCV000216807 likely benign Hereditary cancer-predisposing syndrome 2016-04-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
Invitae RCV000231524 SCV000283277 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-05-25 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 1974 of the BRCA2 protein (p.Thr1974Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 91428). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000436824 SCV000534773 likely benign not specified 2016-12-08 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 RCV000076945 SCV000784847 uncertain significance Breast-ovarian cancer, familial 2 2017-01-04 criteria provided, single submitter clinical testing
GeneKor MSA RCV000166046 SCV000821941 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000076945 SCV000108742 likely benign Breast-ovarian cancer, familial 2 2009-12-07 no assertion criteria provided clinical testing

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