ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3080A>G (p.His1027Arg) (rs786204217)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168340 SCV000219029 uncertain significance Ataxia-telangiectasia syndrome 2019-12-14 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 1027 of the ATM protein (p.His1027Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine 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: 188327). 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.
Ambry Genetics RCV000216063 SCV000276398 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-13 criteria provided, single submitter clinical testing Insufficient or Conflicting Evidence
Fulgent Genetics,Fulgent Genetics RCV000763696 SCV000894576 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2018-10-31 criteria provided, single submitter clinical testing
Color RCV000216063 SCV001354067 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001194328 SCV001363782 uncertain significance not specified 2019-11-05 criteria provided, single submitter clinical testing Variant summary: ATM c.3080A>G (p.His1027Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251156 control chromosomes (one individual in gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3080A>G has been reported in the literature in an individual who was affected with Breast Cancer (Tung_2015). This report does not provide unequivocal conclusions about association of the variant with Ataxia-Telangiectasia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and all cited the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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.