ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4365T>A (p.Ser1455Arg) (rs527471560)

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
Ambry Genetics RCV000165552 SCV000216284 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000165552 SCV000292206 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780910 SCV000918552 uncertain significance not specified 2018-07-13 criteria provided, single submitter clinical testing Variant summary: ATM c.4365T>A (p.Ser1455Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 246182 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4365T>A has been reported in the literature in one individual affected with childhood Hodgkin disease. This report does not provide unequivocal conclusions about association of the variant with Ataxia-Telangiectasia. One study reported the finding of defective ATM-mediated p53 phosphorylation and Chk2 activation in lymphoblastoid cell lines obtained from a patient with childhood Hodgkin disease harboring this variant. However these results cannot be specifically correlated to the pathophysiology and in-vivo effect of this variant as the results obtained could be attributed to another genetic variant unrelated to this specific variant. The authors presented their findings in the context of possible genetic risk factors for childhood Hodgkin disease. To our knowledge, no other direct 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 (2 VUS and 1 likely benign). Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000232578 SCV000282957 likely benign Ataxia-telangiectasia syndrome 2017-12-27 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.