ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7252A>G (p.Arg2418Gly) (rs80358953)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163032 SCV000213520 likely benign Hereditary cancer-predisposing syndrome 2017-08-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting benign classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000113740 SCV000147061 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
Counsyl RCV000113740 SCV000487827 likely benign Breast-ovarian cancer, familial 2 2015-11-18 criteria provided, single submitter clinical testing
GeneDx RCV000443470 SCV000527881 likely benign not specified 2016-05-12 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 RCV000586914 SCV000695051 uncertain significance not provided 2016-12-05 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7252A>G (p.Arg2418Gly) variant involves the alteration of a non-conserved nucleotide. 3/5 in silico tools predict a benign outcome for this variant. This variant is absent in 121330 control chromosomes. The variant has been reported in publications, without strong evidence for causality, and was considered likely benign using a multifactorial based model (Lindor_2012). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign, without evidence to independently evaluate. Taken together, this variant is classified as VUS.
Invitae RCV000045176 SCV000073189 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 2418 of the BRCA2 protein (p.Arg2418Gly). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and glycine. 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. It has been reported in individuals in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 52299). Algorithms developed specifically for the BRCA2 gene (PMID: 21990134, 21990165), as well as general algorithms developed to predict the effect of missense changes on protein structure and function, suggest that this missense change is likely to be tolerated. Also, the glycine 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, this variant is a rare missense change that has been predicted to not affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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