ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2839-3_2839delinsGATACTA (rs786202148)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164817 SCV000215500 likely pathogenic Hereditary cancer-predisposing syndrome 2017-03-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Ambry Genetics RCV000164817 SCV000672712 likely pathogenic Hereditary cancer-predisposing syndrome 2017-05-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Well-characterized mutation at same position,Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Color RCV000164817 SCV000682082 likely pathogenic Hereditary cancer-predisposing syndrome 2018-01-04 criteria provided, single submitter clinical testing
GeneDx RCV000255634 SCV000322093 likely pathogenic not provided 2017-09-18 criteria provided, single submitter clinical testing This combined deletion and insertion is denoted ATM c.2839-3_2839delTAGTinsGATACTA (IVS18-3delTAGTinsGATACTA) at the cDNA level. The surrounding sequence is atct[deltagT][insGATACTA]ATCT, where the capital letters are exonic and lowercase are intronic. The variant spans the intron/exon boundary, removing the canonical splice acceptor site. It is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant, also described as IVS20-3del3ins7 using alternate numbering, has been reported in at least one Hispanic individual with Ataxia-telangiectasia (Mitui 2003). Based on current information, we consider this variant to be likely pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000469912 SCV000918551 likely pathogenic Ataxia-telangiectasia syndrome 2018-07-09 criteria provided, single submitter clinical testing Variant summary: ATM c.2839-3_2839delinsGATACTA is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 3 acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 246128 control chromosomes (gnomAD). The variant, c.2839-3_2839delinsGATACTA, has been reported in the literature in at-least one individual affected with Ataxia-Telangiectasia (LaDuca_2017, Mitui_2003). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely pathogenic." Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000469912 SCV000546815 pathogenic Ataxia-telangiectasia syndrome 2018-09-24 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 18 of the ATM gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with ataxia-telangiectasia (PMID: 12815592). This variant is also known as IVS20-3del3ins7 in the literature. ClinVar contains an entry for this variant (Variation ID: 185405). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as 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.