ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1505C>G (p.Ala502Gly) (rs766595156)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483795 SCV000572404 uncertain significance not provided 2018-10-19 criteria provided, single submitter clinical testing This variant is denoted ATM c.1505C>G at the cDNA level, p.Ala502Gly (A502G) at the protein level, and results in the change of an Alanine to a Glycine (GCT>GGT). This variant was observed in at least one individual with lung squamous cell carcinoma (Lu 2015). ATM Ala502Gly was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located within a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether ATM Ala502Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000566039 SCV000665158 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-11 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;Insufficient evidence
Invitae RCV000688771 SCV000816395 uncertain significance Ataxia-telangiectasia syndrome 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 502 of the ATM protein (p.Ala502Gly). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and glycine. This variant is present in population databases (rs766595156, ExAC 0.01%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 422834). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV000566039 SCV001347300 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-16 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.