In summary, our results link heterozygous CDH1 variants that compromise the tumor suppressor function of E-cadherin and may affect WNT/β-catenin signaling to brain tumor, primarily to OD, risk and tumorigenesis, providing evidence that the phenotype spectrum of rare CDH1 germline variants may extend to brain tumors of neuroepithelial and epithelial origin. The gene discussed is CDH1; the disease is neoplasm.