ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.10160C>G (p.Thr3387Ser) (rs863224584)

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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 RCV000222578 SCV000275484 uncertain significance Hereditary cancer-predisposing syndrome 2015-05-06 criteria provided, single submitter clinical testing
Color RCV000222578 SCV000906832 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-25 criteria provided, single submitter clinical testing
Counsyl RCV000662771 SCV000785572 uncertain significance Breast-ovarian cancer, familial 2 2017-10-05 criteria provided, single submitter clinical testing
GeneDx RCV000613680 SCV000725488 likely benign not specified 2017-11-29 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 RCV000586279 SCV000694498 uncertain significance not provided 2016-10-31 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.10160C>G (p.Thr3387Ser) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121156 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000197203 SCV000254166 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 3387 of the BRCA2 protein (p.Thr3387Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 216239). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine 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 and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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