Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001201291 | SCV001372418 | likely pathogenic | Generalized juvenile polyposis/juvenile polyposis coli | 2020-06-08 | criteria provided, single submitter | clinical testing | Variant summary: SMAD4 c.502G>T (p.Gly168X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251466 control chromosomes (gnomAD). To our knowledge, no occurrence of c.502G>T in individuals affected with Juvenile Polyposis Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. However, several somatic occurrences of this variant have been reported in adenocarcinoma and colorectal cancer samples (PMID: 28125075, 26797410, 10340381). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |