Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| KCCC/NGS Laboratory, |
RCV003237382 | SCV003936021 | pathogenic | Familial cancer of breast | 2023-06-06 | criteria provided, single submitter | clinical testing | A known pathogenic variantin the ATM gene (p.Arg2060fs) in this specimen. This sequence change creates a frameshift starting in exon 42 of the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has no entry in ClinVar. However, ClinVar has an entry for a variant (ClinVar 654478) which creates a frameshift at the same position and reported to be pathogenic. This variant has not been reported in the literature in individuals with ATM-related disease. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic. The cancer risk of individuals heterozygous for an ATM pathogenic variant is approximately four times that of the general population, primarily because of the increased risk for breast cancer. Potentially, it may increase the risk of ovarian cancer. There is insufficient evidence to suggest increased risk for pancreatic cancer. Homozygous or compound heterozygous mutations in the ATM gene are associated with ataxia- telangiectasia (A-T). Classic ataxia-telangiectasia is characterized by progressive cerebellar ataxia beginning between ages 1 and 4 years, oculomotor apraxia, choreoathetosis, telangiectasias of the conjunctivae, immunodeficiency, frequent infections, and an increased risk for malignancy, particularly leukemia and lymphoma. Individuals with A-T are unusually sensitive to ionizing radiation. Non-classic forms of A-T have included adult-onset A-T and A-T with early-onset dystonia. |