Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000815650 | SCV000956111 | likely pathogenic | Hereditary diffuse gastric adenocarcinoma | 2020-08-07 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070). This variant has not been reported in the literature in individuals with CDH1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 2 of the CDH1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Myriad Genetics, |
RCV000815650 | SCV004044196 | likely pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-06-08 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |
Ambry Genetics | RCV004949984 | SCV005558194 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-08 | criteria provided, single submitter | clinical testing | The c.164-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 3 of the CDH1 gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNAdecay; however, direct evidence is unavailable. The exact functional effect of the altered amino acid sequence is unknown. This nucleotide position is highly conserved in available vertebrate species. Based on the available evidence, the clinical significance of this variant remains unclear. |