ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.7928-2A>T (rs864622610)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205665 SCV000261323 likely pathogenic Ataxia-telangiectasia syndrome 2015-10-16 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 53. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in ATM are known to be pathogenic (PMID: 10817650, 19781682). Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this intronic variant may alter consensus mRNA splicing, leading to the out-of-frame skipping of exon 54. However, these predictors also suggest that alternative splicing could occur at an activated cryptic splice site 3 nucleotides into exon 54, leading to two amino acid changes with uncertain impact on protein function (p.Lys2643_Gly2644delinsSer). Alternatively, splicing could arise at a naturally-occurring cryptic splice site 34 nucleotides upstream of exon 54, leading to the out-of-frame premature truncation of the ATM protein. However, these predictions have not been confirmed by published transcriptional studies. Despite the uncertainty about the effect this variant will have on mRNA splicing and protein function, and in the absence of experimental evidence, it has been classified as Likely Pathogenic.

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.