ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.446A>G (p.Glu149Gly)

gnomAD frequency: 0.00001  dbSNP: rs786203794
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167254 SCV000218094 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-07 criteria provided, single submitter clinical testing The p.E149G variant (also known as c.446A>G), located in coding exon 3 of the CHEK2 gene, results from an A to G substitution at nucleotide position 446. The glutamic acid at codon 149 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000700163 SCV000828908 uncertain significance Familial cancer of breast 2023-04-19 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 187519). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 149 of the CHEK2 protein (p.Glu149Gly).
GeneDx RCV001753573 SCV002006658 uncertain significance not provided 2019-12-11 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek 2016); Has not been previously published as pathogenic or benign to our knowledge; Also known as c.575A>G, p.E192G

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