Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000698373 | SCV000827033 | pathogenic | Ataxia-telangiectasia syndrome | 2023-09-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr2049*) 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: 576000). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001545926 | SCV001765350 | pathogenic | not provided | 2024-08-29 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 30287823, 29470806) |
| Ambry Genetics | RCV002352170 | SCV002654918 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-05-21 | criteria provided, single submitter | clinical testing | The c.6146_6147delAT pathogenic mutation, located in coding exon 41 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 6146 to 6147, causing a translational frameshift with a predicted alternate stop codon (p.Y2049*). This mutation was observed with an allele frequency of 0.00014 in 7051 unselected female breast cancer patients and was not observed in 11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This mutation was also observed in a study of 1010 unrelated Indian patients with breast and/or ovarian cancer (Singh J et al. Breast Cancer Res Treat, 2018 Jul;170:189-196). In addition to the clinical data presented in the literature, 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. |
| Myriad Genetics, |
RCV004026443 | SCV004932203 | pathogenic | Familial cancer of breast | 2024-01-29 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
| Baylor Genetics | RCV004026443 | SCV005056976 | pathogenic | Familial cancer of breast | 2024-02-17 | criteria provided, single submitter | clinical testing |