Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001043381 | SCV001207125 | pathogenic | Ataxia-telangiectasia syndrome | 2022-11-28 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr714Leufs*21) 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 has not been reported in the literature in individuals affected with ATM-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 841206). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001043381 | SCV001339134 | likely pathogenic | Ataxia-telangiectasia syndrome | 2020-03-20 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.2140delA (p.Thr714LeufsX21) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249916 control chromosomes. c.2140delA has not been reported in the literature in individuals affected with Ataxia-Telangiectasia or breast cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Ambry Genetics | RCV003363062 | SCV004053919 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-07-06 | criteria provided, single submitter | clinical testing | The c.2140delA variant, located in coding exon 13 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 2140, causing a translational frameshift with a predicted alternate stop codon (p.T714Lfs*21). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Laboratory for Genotyping Development, |
RCV003160305 | SCV002758392 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |