Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001347320 | SCV001541575 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-05-19 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 14 of the CDH1 gene. It does not directly change the encoded amino acid sequence of the CDH1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1043240). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV004036515 | SCV005022315 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-26 | criteria provided, single submitter | clinical testing | The c.2295+4G>A intronic variant results from a G to A substitution 4 nucleotides after coding exon 14 in the CDH1 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Myriad Genetics, |
RCV001347320 | SCV005403901 | likely benign | Hereditary diffuse gastric adenocarcinoma | 2024-09-23 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. |