ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3515C>G (p.Ser1172Trp) (rs80358600)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044212 SCV000072225 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-03-28 criteria provided, single submitter clinical testing This sequence change replaces serine with tryptophan at codon 1172 of the BRCA2 protein (p.Ser1172Trp). The serine residue is moderately conserved and there is a large physicochemical difference between serine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with a personal and/or family history of breast and/or ovarian cancer (PMID: 25896959). ClinVar contains an entry for this variant (Variation ID: 51480). 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: "Deleterious"; 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.
Ambry Genetics RCV000222703 SCV000275647 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000077305 SCV000488043 uncertain significance Breast-ovarian cancer, familial 2 2015-12-16 criteria provided, single submitter clinical testing
Color RCV000222703 SCV000537557 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781071 SCV000918879 uncertain significance not specified 2018-03-26 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3515C>G (p.Ser1172Trp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 276524 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.3515C>G, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Wong-Brown_2015, D'Argenio_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as "uncertain significance." Based on the evidence outlined above, the variant was classified as uncertain significance.
Sharing Clinical Reports Project (SCRP) RCV000077305 SCV000109102 uncertain significance Breast-ovarian cancer, familial 2 2012-07-26 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077305 SCV000146250 uncertain significance Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing

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