ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3344C>G (p.Ser1115Cys) (rs879255448)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000572645 SCV000661256 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Color RCV000572645 SCV000683550 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-31 criteria provided, single submitter clinical testing
Invitae RCV000637640 SCV000759107 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-11-21 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 1115 of the BRCA2 protein (p.Ser1115Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. 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: 252828). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Integrated Genetics/Laboratory Corporation of America RCV000781124 SCV000918972 uncertain significance not specified 2018-05-21 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3344C>G (p.Ser1115Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 119276 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3344C>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Sharing Clinical Reports Project (SCRP) RCV000239210 SCV000297431 uncertain significance Breast-ovarian cancer, familial 2 2008-09-23 no assertion criteria provided clinical testing

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