Submissions for variant NM_007194.4(CHEK2):c.494G>A (p.Gly165Asp)

dbSNP: rs876660846

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000221086	SCV000278598	uncertain significance	Hereditary cancer-predisposing syndrome	2021-08-18	criteria provided, single submitter	clinical testing	The p.G165D variant (also known as c.494G>A), located in coding exon 3 of the CHEK2 gene, results from a G to A substitution at nucleotide position 494. The glycine at codon 165 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV000465836	SCV000550479	uncertain significance	Familial cancer of breast	2023-06-21	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 234097). 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. This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 165 of the CHEK2 protein (p.Gly165Asp).
GeneDx	RCV000485481	SCV000568048	uncertain significance	not provided	2022-12-22	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22419737, 19782031)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798724	SCV002043406	uncertain significance	Breast and/or ovarian cancer	2020-03-20	criteria provided, single submitter	clinical testing