ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4909+1G>A

gnomAD frequency: 0.00001  dbSNP: rs756987454
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 RCV000566360 SCV000660621 pathogenic Hereditary cancer-predisposing syndrome 2017-04-03 criteria provided, single submitter clinical testing The c.4909+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 31 of the ATM gene. This alteration was observed in the homozygous state in two apparently unrelated individuals with ataxia-telangiectasia (Sandoval N et al. Hum. Mol. Genet. 1999 Jan;8(1):69-79). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV000628067 SCV000748956 pathogenic Ataxia-telangiectasia syndrome 2021-04-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been reported as homozygous in two apparently unrelated individuals affected with ataxia-telangiectasia, and as heterozygous in an individual affected with breast cancer (PMID: 9887333, 26534844). ClinVar contains an entry for this variant (Variation ID: 478991). This variant is present in population databases (rs756987454, ExAC 0.001%). This sequence change affects a donor splice site in intron 32 of the ATM gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
Myriad Genetics, Inc. RCV004024452 SCV004933616 pathogenic Familial cancer of breast 2024-01-25 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 29489040, 9887333].
Natera, Inc. RCV000628067 SCV001462344 pathogenic Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided 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.