Submissions for variant NM_007194.4(CHEK2):c.920G>A (p.Gly307Glu)

dbSNP: rs876661053

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000215327	SCV000279369	uncertain significance	not provided	2016-02-29	criteria provided, single submitter	clinical testing	This variant is denoted CHEK2 c.920G>A at the cDNA level, p.Gly307Glu (G307E) at the protein level, and results in the change of a Glycine to a Glutamic Acid (GGA>GAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. CHEK2 Gly307Glu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Glycine and Glutamic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. CHEK2 Gly307Glu occurs at a position that is conserved across species and is located in the protein kinase domain and an ATP binding region (Roeb 2012, UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether CHEK2 Gly307Glu is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae	RCV000476255	SCV000550426	uncertain significance	Familial cancer of breast	2024-01-19	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 307 of the CHEK2 protein (p.Gly307Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 234497). 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. 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.
Counsyl	RCV000476255	SCV000785898	uncertain significance	Familial cancer of breast	2018-01-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001019005	SCV001180306	uncertain significance	Hereditary cancer-predisposing syndrome	2023-06-14	criteria provided, single submitter	clinical testing	The p.G307E variant (also known as c.920G>A), located in coding exon 8 of the CHEK2 gene, results from a G to A substitution at nucleotide position 920. The glycine at codon 307 is replaced by glutamic acid, 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.
Fulgent Genetics, Fulgent Genetics	RCV002500740	SCV002814717	uncertain significance	Familial cancer of breast; Li-Fraumeni syndrome 2; Bone osteosarcoma; Malignant tumor of prostate; Colorectal cancer	2022-04-10	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000476255	SCV004020153	uncertain significance	Familial cancer of breast	2023-03-08	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics	RCV000476255	SCV004217500	uncertain significance	Familial cancer of breast	2023-10-16	criteria provided, single submitter	clinical testing