ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2946A>G (p.Ile982Met) (rs80358541)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131646 SCV000186673 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000031391 SCV000146145 uncertain significance Breast-ovarian cancer, familial 2 2002-06-20 no assertion criteria provided clinical testing
Color RCV000131646 SCV000910934 likely benign Hereditary cancer-predisposing syndrome 2016-01-22 criteria provided, single submitter clinical testing
GeneDx RCV000590161 SCV000210297 uncertain significance not provided 2018-06-29 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.2946A>G at the cDNA level, p.Ile982Met (I982M) at the protein level, and results in the change of an Isoleucine to a Methionine (ATA>ATG). Using alternate nomenclature, this variant would be defined as BRCA2 3174A>G. This variant has been observed in at least one individual with early onset breast cancer (Lee 2008). BRCA2 Ile982Met was observed at an allele frequency of 0.06% (20/33,344) in individuals of Latino ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Ile982Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000590161 SCV000694652 uncertain significance not provided 2016-04-18 criteria provided, single submitter clinical testing Variant summary: The c.2946A>G variant affects a non-conserved nucleotide, resulting in amino acid change from Ile to Met. 4/5 in-silico tools predict this variant to be benign. This variant is found in 6/120302 control chromosomes at a frequency of 0.0000499, which does not exceed the maximal expected frequency of a pathogenic allele (0.0007503) in this gene. It was mainly found in Latino cohort with an allele frequency of 0.0004 (5/11500 chromosomes), suggesting that it may be a rare polymorphism in this population; however, there are no other supporting evidences for this. The variant has been reported in one Hispanic breast cancer patient (Lee 2008) without strong evidence for causality. It has also been reported in two individuals undergoing BRCA1/2 testing in BIC. Multiple clinical labs have classified this variant as having uncertain significance. Because of the absence of sufficient clinical information and the lack of functional studies, the variant has currently been classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000203664 SCV000072104 likely benign Hereditary breast and ovarian cancer syndrome 2018-01-22 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000044091 SCV000296677 uncertain significance not specified 2017-05-23 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031391 SCV000053996 likely benign Breast-ovarian cancer, familial 2 2014-02-19 no assertion criteria provided clinical testing

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