Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328317 | SCV001437611 | likely pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-24 | reviewed by expert panel | curation | The c.1320+1G>C variant occurs at the canonical splice donor site of exon 9 (PVS1_strong, PM5_supporting). This variant is absent from populations in gnomAD (PM2_supporting; http://gnomad.broadinstitute.org). Splicing analysis in vitro has shown that the C allele results in skipping of exon 9, producing an abnormal in-frame transcript (PS3_supporting; PMID: 8033105, 28301459). Furthermore, this variant has been observed in at least one family meeting IGCLC criteria for HDGC (PS4_supporting; SCV000322628.7). In summary, this variant meets criteria to be classified as likely pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1_strong, PM2_supporting, PS3_supporting, PS4_supporting, PM5_supporting. |
Gene |
RCV000255500 | SCV000322628 | pathogenic | not provided | 2017-05-15 | criteria provided, single submitter | clinical testing | This variant is denoted CDH1 c.1320+1G>C or IVS9+1G>C and consists of a G>C nucleotide substitution at the +1 position of intron 9 of the CDH1 gene. This variant destroys a canonical splice donor site and has been shown to result in in-frame skipping of exon 9 (Becker 1994). Even though this variant results in an in-frame transcript, this single exon deletion would result in the loss of 61 residues, which are located within the cadherin 3 domain (UniProt). Based on the currently available information, we consider CDH1 c.1320+1G>C to be pathogenic. |
Myriad Genetics, |
RCV003335297 | SCV004045202 | likely pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-06-28 | 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. |
OMIM | RCV000505772 | SCV000599984 | pathogenic | Blepharocheilodontic syndrome 1 | 2017-09-20 | no assertion criteria provided | literature only |