Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001246756 | SCV001420138 | pathogenic | Ataxia-telangiectasia syndrome | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg2612Glyfs*19) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 971065). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002411907 | SCV002669267 | pathogenic | Hereditary cancer-predisposing syndrome | 2015-11-19 | criteria provided, single submitter | clinical testing | The c.7834delA pathogenic mutation, located in coding exon 52 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 7834, causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001246756 | SCV004020779 | pathogenic | Ataxia-telangiectasia syndrome | 2023-06-29 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.7834delA (p.Arg2612GlyfsX19) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 250816 control chromosomes (gnomAD). To our knowledge, no occurrence of c.7834delA in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |