Submissions for variant NM_000051.4(ATM):c.6260A>G (p.Glu2087Gly)

dbSNP: rs1565503023

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000706594	SCV000835654	uncertain significance	Ataxia-telangiectasia syndrome	2023-05-30	criteria provided, single submitter	clinical testing	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 tolerated. ClinVar contains an entry for this variant (Variation ID: 582503). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2087 of the ATM protein (p.Glu2087Gly).
Mendelics	RCV000706594	SCV000838569	uncertain significance	Ataxia-telangiectasia syndrome	2018-07-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000773177	SCV000906738	uncertain significance	Hereditary cancer-predisposing syndrome	2022-03-07	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with glycine at codon 2087 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 not been identified 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.
Ambry Genetics	RCV000773177	SCV001187174	uncertain significance	Hereditary cancer-predisposing syndrome	2020-11-06	criteria provided, single submitter	clinical testing	The p.E2087G variant (also known as c.6260A>G), located in coding exon 42 of the ATM gene, results from an A to G substitution at nucleotide position 6260. The glutamic acid at codon 2087 is replaced by glycine, 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.
GeneDx	RCV003442055	SCV004169925	uncertain significance	not provided	2023-04-11	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23532176)
Natera, Inc.	RCV000706594	SCV002081068	uncertain significance	Ataxia-telangiectasia syndrome	2021-01-12	no assertion criteria provided	clinical testing