Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000802589 | SCV000942426 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-03-28 | criteria provided, single submitter | clinical testing | 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. Deletions of the entire EPCAM gene have been reported in an individual affected with a Lynch syndrome-associated cancer and/or colorectal polyps (PMID: 25980754), and an individual with autosomal recessive congenital tufting enteropathy (PMID: 24142340). Deletions involving the 3 region of the EPCAM gene (minimally, exon 9) are known to cause Lynch syndrome. These deletions lead to transcriptional read-through from the EPCAM promoter into the adjacent MSH2 gene, resulting in hypermethylation of the MSH2 promoter and silencing of MSH2 expression (PMID: 19098912, 19177550, 21309036). However, without knowing the 5' boundary of this event, it is not known if this variant will cause MSH2 silencing. For these reasons, this variant has been classified as Pathogenic for congenital tufting enteropathy. However, it is not currently known if this specific variant confers risk for Lynch syndrome. |