ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6943A>C (p.Ile2315Leu) (rs80358918)

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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 RCV000130766 SCV000185659 likely benign Hereditary cancer-predisposing syndrome 2018-04-11 criteria provided, single submitter clinical testing Does not segregate with disease in family study (genes with incomplete penetrance);In silico models in agreement (benign);No disease association in small case-control study;Other data supporting benign classification;Structural Evidence
GeneDx RCV000212254 SCV000210640 likely benign not specified 2016-05-16 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212254 SCV000600725 uncertain significance not specified 2017-05-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587113 SCV000695011 uncertain significance not provided 2016-12-22 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.6943A>C (p.Ile2315Leu) variant involves the alteration of a not conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNP&Go not captured due to low reliability index). This variant was found in 10/116052 control chromosomes at a frequency of 0.0000862, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). This variant has been reported in multiple affected individuals without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS.
Color Health, Inc RCV000130766 SCV000911098 likely benign Hereditary cancer-predisposing syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV001345343 SCV001539454 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-11-02 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with leucine at codon 2315 of the BRCA2 protein (p.Ile2315Leu). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is present in population databases (rs80358918, ExAC 0.02%). This variant has been reported in individuals with a personal and/or family history of breast cancer (PMID: 22752604, 21638052, 26733283). This variant is also known as 7171A>C in the literature. ClinVar contains an entry for this variant (Variation ID: 52223). 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, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113675 SCV000146975 uncertain significance Breast-ovarian cancer, familial 2 1999-04-12 no assertion criteria provided clinical testing

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