Submissions for variant NM_000051.4(ATM):c.6214G>A (p.Gly2072Arg)

dbSNP: rs1555114568

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000533324	SCV000622650	uncertain significance	Ataxia-telangiectasia syndrome	2024-01-21	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2072 of the ATM protein (p.Gly2072Arg). This variant is not present in population databases (gnomAD no frequency). 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: 453620). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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	RCV000561953	SCV000672654	uncertain significance	Hereditary cancer-predisposing syndrome	2023-08-30	criteria provided, single submitter	clinical testing	The p.G2072R variant (also known as c.6214G>A), located in coding exon 42 of the ATM gene, results from a G to A substitution at nucleotide position 6214. The glycine at codon 2072 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly 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.
Color Diagnostics, LLC DBA Color Health	RCV000561953	SCV000912992	uncertain significance	Hereditary cancer-predisposing syndrome	2020-05-11	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with arginine at codon 2072 of the ATM protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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.
Baylor Genetics	RCV004568683	SCV005057139	uncertain significance	Familial cancer of breast	2023-12-19	criteria provided, single submitter	clinical testing
GeneDx	RCV004592513	SCV005078394	uncertain significance	not provided	2023-10-04	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; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 23532176)