Submissions for variant NM_000051.4(ATM):c.7487G>A (p.Gly2496Glu)

dbSNP: rs764478418

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000215037	SCV000274955	uncertain significance	Hereditary cancer-predisposing syndrome	2024-06-24	criteria provided, single submitter	clinical testing	The p.G2496E variant (also known as c.7487G>A), located in coding exon 49 of the ATM gene, results from a G to A substitution at nucleotide position 7487. The glycine at codon 2496 is replaced by glutamic acid, an amino acid with similar properties. This alteration was identified in an individual diagnosed with ovarian cancer (Fu K et al. Sci Rep, 2024 Mar;14:6702). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001042097	SCV001205761	uncertain significance	Ataxia-telangiectasia syndrome	2022-06-20	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 2496 of the ATM protein (p.Gly2496Glu). This variant is present in population databases (rs764478418, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 231188). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM protein function. 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.
Color Diagnostics, LLC DBA Color Health	RCV000215037	SCV001339685	uncertain significance	Hereditary cancer-predisposing syndrome	2019-01-31	criteria provided, single submitter	clinical testing
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153502	SCV003843855	benign	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001042097	SCV002080666	uncertain significance	Ataxia-telangiectasia syndrome	2021-07-24	no assertion criteria provided	clinical testing