The CDH1 is a well-known gene causing hereditary diffuse gastric cancer, but there are few clinical studies about familial gastric cancer caused by other genes. Carriers with non-CDH1 mutations lack information to guide risk-reducing surgery and risk assessment. In order to identify other suspect genes of hereditary diffuse gastric cancer, a UK familial gastric cancer research team conducted whole-exome sequencing from 28 cases diagnosed with hereditary diffuse gastric cancer and 11 unaffected first-degree relatives in 22 families without pathogenic CDH1 variants. They found several germline mutations, in cancer suspect genes or less studied DNA repair genes, from 6 families with hereditary diffuse gastric cancer. One of those mutations was a frameshift deletion in PALB2. This variant was identified in a case from a family with a history of gastric and breast cancer. One frameshift insertion and one start-codon loss in MSH2 were found from 2 unrelated patients. A unique combination of variants in the DNA repair genes ATR and NBN was found in a family. In the DNA repair gene RECQL5, one missense and one splice-site variant were identified in two unrelated families. This study helps us realize the role of PALB2 in hereditary diffuse gastric cancer without CDH1 mutation, as well as identify new suspect genes related to the disease.