Submissions for variant NM_000051.4(ATM):c.8405A>G (p.Gln2802Arg)

gnomAD frequency: 0.00002  dbSNP: rs730881324

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000159660	SCV000209656	uncertain significance	not provided	2019-02-28	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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
Labcorp Genetics (formerly Invitae), Labcorp	RCV000464909	SCV000546903	uncertain significance	Ataxia-telangiectasia syndrome	2022-10-21	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 2802 of the ATM protein (p.Gln2802Arg). This variant is present in population databases (rs730881324, gnomAD 0.009%). 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: 181897). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Ambry Genetics	RCV000562069	SCV000672620	uncertain significance	Hereditary cancer-predisposing syndrome	2022-11-02	criteria provided, single submitter	clinical testing	The p.Q2802R variant (also known as c.8405A>G), located in coding exon 56 of the ATM gene, results from an A to G substitution at nucleotide position 8405. The glutamine at codon 2802 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved through reptiles, but is not conserved in lower species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV000562069	SCV000687828	uncertain significance	Hereditary cancer-predisposing syndrome	2021-10-13	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with arginine at codon 2802 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 4/251168 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Athena Diagnostics	RCV000159660	SCV002771760	uncertain significance	not provided	2021-12-02	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003467222	SCV004207047	uncertain significance	Familial cancer of breast	2023-10-06	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000464909	SCV002079516	uncertain significance	Ataxia-telangiectasia syndrome	2021-08-16	no assertion criteria provided	clinical testing