ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2638+2T>C (rs587779826)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000115162 SCV000214719 likely pathogenic Hereditary cancer-predisposing syndrome 2017-09-27 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
Color RCV000115162 SCV000682067 likely pathogenic Hereditary cancer-predisposing syndrome 2018-08-22 criteria provided, single submitter clinical testing
Counsyl RCV000477335 SCV000794012 pathogenic Ataxia-telangiectasia syndrome 2017-09-06 criteria provided, single submitter clinical testing
GeneDx RCV000211986 SCV000149071 pathogenic not provided 2018-06-05 criteria provided, single submitter clinical testing This pathogenic variant is denoted ATM c.2638+2T>C or IVS17+2T>C and consists of a T>C nucleotide substitution at the +2 position of intron 17 of the ATM gene. The variant destroys a canonical splice donor site and 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 has been reported in an individual with melanoma, thyroid cancer, kidney cancer, and polyps who was undergoing hereditary cancer multigene panel testing (Shirts 2016). Additionally, a different nucleotide change at the same position, ATM c.2638+2T>G, reported as IVS19+2T>G using alternate exon numbering, was observed in trans with ATM Val2716Ala in four adult sisters with atypical ataxia-telangiectasia (Méneret 2014). Based on the current evidence, we consider ATM c.2638+2T>C to be pathogenic.
Invitae RCV000477335 SCV000547102 pathogenic Ataxia-telangiectasia syndrome 2018-09-23 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 17 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 observed in an individual affected with breast cancer (PMID: 26681312), and an individual affected with melanoma, thyroid and kidney cancer (PMID: 26845104). ClinVar contains an entry for this variant (Variation ID: 127357). A different variant affecting this nucleotide (c.2638+2T>G, also known as VS19+2T>G) has been determined to be pathogenic (PMID: 25122203). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. 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.
PreventionGenetics RCV000211986 SCV000805523 likely pathogenic not provided 2017-10-27 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine,University of Washington RCV000115162 SCV000266015 likely pathogenic Hereditary cancer-predisposing syndrome 2015-11-20 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.