ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.901+2T>C

dbSNP: rs1218815157
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000777332 SCV000913194 likely pathogenic Hereditary cancer-predisposing syndrome 2020-04-24 criteria provided, single submitter clinical testing This variant causes a T to C nucleotide substitution at the +2 position of intron 7 of the ATM gene. Splice site prediction tools suggest that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic.
Ambry Genetics RCV000777332 SCV002683497 pathogenic Hereditary cancer-predisposing syndrome 2020-08-06 criteria provided, single submitter clinical testing The c.901+2T>C intronic pathogenic mutation results from a T to C substitution two nucleotides after coding exon 6 in the ATM gene. Though this exact alteration has not been reported in the literature, two other alterations impacting the same donor site (c.901+1G>A and c.901+2T>A) have been shown to have a similar impact on splicing and have been identified in individuals with ataxia telangiectasia (Mitui M et al. Hum. Mutat. 2003 Jul;22(1):43-50; Laake K et al. Hum. Mutat. 2000 Sep;16(3):232-46; Ambry internal data). In silico splice site analysis predicts that the c.901+2T>C alteration will weaken the native splice donor site. 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.

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.