ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5839C>T (p.Pro1947Ser) (rs80358812)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044772 SCV000072785 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-30 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 1947 of the BRCA2 protein (p.Pro1947Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs80358812, ExAC 0.02%). This variant has been reported in the literature in individuals affected with breast cancer (PMID: 28664449). ClinVar contains an entry for this variant (Variation ID: 51950). 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.
Ambry Genetics RCV000132548 SCV000187646 likely benign Hereditary cancer-predisposing syndrome 2016-11-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,In silico models in agreement (benign)
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768631 SCV000324875 uncertain significance Breast and/or ovarian cancer 2015-08-11 criteria provided, single submitter clinical testing
Counsyl RCV000113492 SCV000487847 uncertain significance Breast-ovarian cancer, familial 2 2015-11-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781083 SCV000918894 uncertain significance not specified 2018-12-24 criteria provided, single submitter clinical testing Variant summary: The variant, BRCA2 c.5839C>T (p.Pro1947Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 245988 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.5839C>T has been reported in the literature in individuals affected with Breast and Ovarian Cancer (LiA_2018, Chan _2018, Li_2017). These reports 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. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Two labs have classified as uncertain significance and one as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985552 SCV001133842 uncertain significance not provided 2019-06-13 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113492 SCV000146710 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing

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