ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.8405A>G (p.Gln2802Arg) (rs730881324)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562069 SCV000672620 uncertain significance Hereditary cancer-predisposing syndrome 2016-04-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000562069 SCV000687828 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-14 criteria provided, single submitter clinical testing
GeneDx RCV000159660 SCV000209656 uncertain significance not provided 2017-05-25 criteria provided, single submitter clinical testing This variant is denoted ATM c.8405A>G at the cDNA level, p.Gln2802Arg (Q2802R) at the protein level, and results in the change of a Glutamine to an Arginine (CAA>CGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Gln2802Arg was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Glutamine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. ATM Gln2802Arg occurs at a position that is conserved in mammals and is located in the kinase domain (Stracker 2013). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether ATM Gln2802Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000464909 SCV000546903 uncertain significance Ataxia-telangiectasia syndrome 2018-06-01 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 2802 of the ATM protein (p.Gln2802Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related disease. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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