ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3451A>G (p.Ile1151Val) (rs80358591)

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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 RCV000214609 SCV000277208 uncertain significance Hereditary cancer-predisposing syndrome 2015-09-03 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113178 SCV000146236 uncertain significance Breast-ovarian cancer, familial 2 2001-10-29 no assertion criteria provided clinical testing
Color RCV000214609 SCV000906682 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-31 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000502245 SCV000591862 uncertain significance not specified 2015-05-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000502245 SCV000916861 uncertain significance not specified 2018-02-23 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3451A>G (p.Ile1151Val) alters a non-conserved nucleotide resulting in a conservative amino acid change in the BRCA2 repeat region (IPR002093) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 245786 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.3451A>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three 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.
Invitae RCV000044197 SCV000072210 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-12-12 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 1151 of the BRCA2 protein (p.Ile1151Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs80358591, ExAC 0.002%). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 51467). 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 valine 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.
Sharing Clinical Reports Project (SCRP) RCV000113178 SCV000297519 uncertain significance Breast-ovarian cancer, familial 2 2013-08-22 no assertion criteria provided clinical testing

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