ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6118A>G (p.Ile2040Val) (rs80358850)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165889 SCV000216642 uncertain significance Hereditary cancer-predisposing syndrome 2016-08-07 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000416535 SCV000494422 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-09-29 criteria provided, single submitter clinical testing Variant Summary: BRCA2 c.6118A>G is a missense mutation that occurs at a non-conserved position and 4/4 in silico tools predict a neutral outcome. The variant has not been cited in the literature or found in controls, including the large and diverse ExAC cohort (~0/120840). Additionally, multiple reputable diagnostic centers classify the variant as a VUS. Taken together, this BRCA2 missense muation is classified as a VUS until more information is available.
Invitae RCV000416535 SCV000813694 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-06-21 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 2040 of the BRCA2 protein (p.Ile2040Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 96833). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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) RCV000082954 SCV000115028 uncertain significance Breast-ovarian cancer, familial 2 2013-06-07 no assertion criteria provided clinical testing

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