ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9728C>T (p.Pro3243Leu) (rs80359241)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000045892 SCV000602772 uncertain significance not specified 2016-08-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000166251 SCV000217031 likely benign Hereditary cancer-predisposing syndrome 2017-01-12 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)
Breast Cancer Information Core (BIC) (BRCA2) RCV000031845 SCV000147704 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000166251 SCV000902988 likely benign Hereditary cancer-predisposing syndrome 2017-04-03 criteria provided, single submitter clinical testing
Counsyl RCV000031845 SCV000487774 uncertain significance Breast-ovarian cancer, familial 2 2015-11-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000045892 SCV000592305 uncertain significance not specified 2015-02-17 criteria provided, single submitter clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735633 SCV000863771 uncertain significance Breast and/or ovarian cancer 2014-11-21 no assertion criteria provided clinical testing
GeneDx RCV000045892 SCV000210692 likely benign not specified 2017-08-24 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 RCV000587179 SCV000695266 uncertain significance not provided 2017-04-14 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9728C>T (p.Pro3243Leu) variant involves the alteration of a non-conserved nucleotide. 3/5 in silico tools predict a damaging outcome. This variant was found in 2/121336 control chromosomes at a frequency of 0.0000165, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). This variant has been reported in one OvC patient without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/VUS, all without evidence to independently evaluate. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000167844 SCV000073905 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 3243 of the BRCA2 protein (p.Pro3243Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs80359241, ExAC 0.02%). This variant has been reported in the literature in an individual affected with breast cancer (PMID: 21218378). ClinVar contains an entry for this variant (Variation ID: 38262). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on BRCA2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031845 SCV000296526 uncertain significance Breast-ovarian cancer, familial 2 2016-04-27 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031845 SCV000054453 benign Breast-ovarian cancer, familial 2 2010-09-01 no assertion criteria provided clinical testing

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