Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002408307 | SCV002722002 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-04-08 | criteria provided, single submitter | clinical testing | The c.1904_1905delAC pathogenic mutation, located in coding exon 12 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 1904 to 1905, causing a translational frameshift with a predicted alternate stop codon (p.H635Pfs*5). 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 Molecular Medicine, |
RCV004017933 | SCV004848774 | likely pathogenic | Familial cancer of breast | 2022-08-30 | criteria provided, single submitter | clinical testing | The p.His635ProfsX5 variant in ATM has not been reported in individuals with disease and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 635 and leads to a premature termination codon 5 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the ATM gene is an established disease mechanism in autosomal dominant hereditary breast carcinoma. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant hereditary breast carcinoma ACMG/AMP criteria applied: PM2_supporting, PVS1. |