ClinVar Genomic variation as it relates to human health

A gross deletion of the genomic region encompassing the full coding sequence of the EPCAM gene has been identified. The 5’ boundary of this event is unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. If MSH2 has been tested and no copy number events are reported for it, then the 3' boundary of this event lies between the EPCAM and MSH2 genes. If MSH2 has not been tested, the 3' end of this event is unknown as it extends beyond the assayed region of this test. This is expected to result in an absent or disrupted protein product. Loss-of-function variants in EPCAM are known to be pathogenic. Deletion of the entire EPCAM gene has been reported in an individual affected with a Lynch syndrome-associated cancer and/or colorectal polyps (PMID: 25980754), as well as in an individual affected with autosomal recessive congenital tufting enteropathy (PMID: 24142340). In addition, deletions of EPCAM extending to the adjacent MSH2 gene have been reported in individuals with Lynch syndrome (PMID: 16086322, 22658618), and deletions involving the 3' end of the EPCAM gene are known to cause Lynch syndrome through the mechanism of transcriptional read-through resulting in silencing of the adjacent MSH2 gene (PMID: 21145788). For these reasons, this variant has been classified as Pathogenic.