ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000016.9) (NC_000016.10)
Evidence for haploinsufficiency phenotype
PubMed ID Description
26182300 Hansford et al (2015) reported a large series of CDH1 mutation carriers including a new patient with a deletion encompassing exons 1 and 2, and provided a review of CDH1 germline mutations including 126 pathogenic variants (see eTable1). The majority of reported pathogenic alterations in HDGC are loss-of-function-type, including sequence-level alterations (nonsense, frameshift) and larger, exon-level deletions.
24037103 Yamada et al (2014) detected a 275-kb deletion involving exons 7?16 of CDH1 in a Japanese HDGC family using comparative genomic hybridization (CGH) analysis. The proband (55 year-old female) and her affected son (31 year-old) both carried this deletion.
19168852 Oliveira et al (2009) reported 5 intragenic (exon-level) deletions of CDH1 in their study of a large cohort of patients (160 families) with hereditary diffuse gastric cancer (HDGC). In sum, CDH1 alterations were identified in 45.6% (73/160) patients.

Haploinsufficiency phenotype comments:

Constitutional (germline) mutation and deletion involving the gene E-cadherin (CDH1) is associated with autosomal dominant hereditary diffuse gastric cancer (HDGC). HDGC is a cancer predisposition syndrome associated with the development of diffuse gastric cancer (DGC) in men and women and lobular breast cancer (LBC) in women. Penetrance estimates vary across studies-see PMIDs 26182300, 20301318. The majority of CDH1 mutations reported in HDGC are loss-of-function-type, including sequence-level mutations (nonsense, frameshift) and intragenic, exon-level deletions. No genotype-phenotype correlations have been reported to date. Germline whole gene deletion of CDH1 has been reported in one individual with Esophagogastric Adenocarcinoma. (PMID: 26556299)

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

There is no evidence linking triplosensitivity of CDH1 to clinical phenotypes.