ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2524G>C (p.Val842Leu) (rs587782454)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131527 SCV000186521 uncertain significance Hereditary cancer-predisposing syndrome 2016-04-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Insufficient or conflicting evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV000462356 SCV000549660 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-02-13 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 842 of the BRCA2 protein (p.Val842Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs587782454, ExAC 0.03%) but has not been reported in the literature in individuals with a BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 142422). 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 leucine 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.
Genetic Services Laboratory, University of Chicago RCV000501377 SCV000593742 uncertain significance not specified 2017-01-12 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758877 SCV000887779 uncertain significance not provided 2018-05-03 criteria provided, single submitter clinical testing
Color RCV000131527 SCV000906044 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000501377 SCV000918846 uncertain significance not specified 2018-01-15 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.2524G>C (p.Val842Leu) variant involves the alteration of a non-conserved nucleotide. 4/5 in silico tools predict a benign outcome for this variant. This variant was found in 7/242908 control chromosomes at a frequency of 0.0000288, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance, while one has classified it as likely benign, without evidence to independently evaluate. 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.
Sharing Clinical Reports Project (SCRP) RCV000238749 SCV000297512 likely benign Breast-ovarian cancer, familial 2 2010-01-30 no assertion criteria provided clinical testing

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