Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000568931 | SCV000676329 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2017-05-22 | criteria provided, single submitter | clinical testing | The c.8850+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 60 of the ATM gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
CHEO Genetics Diagnostic Laboratory, |
RCV003492107 | SCV004239979 | pathogenic | Breast and/or ovarian cancer | 2022-09-02 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000568931 | SCV004361931 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-03-29 | criteria provided, single submitter | clinical testing | This variant causes a G to A nucleotide substitution at the +1 position of intron 61 of the ATM gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. This variant has been reported in an individual affected with pancreatic ductal adenocarcinomas (PMID: 30836094) and in an individual affected with breast cancer who also carried two co-variants in MLH1 gene and PALB2 gene (DOI: 10.1101/2022.05.31.22275080). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. |