Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001031781 | SCV001195087 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-03-25 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 8-9 of the EPCAM gene. The 5' boundary is likely confined to intron 7. 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 through the termination codon beyond the assayed region for this gene. Similar deletions of exons 8-9 have been reported in individuals and families affected with Lynch syndrome (PMID: 23454724, 21309036, 21227399, 20864635, 22243433). 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). For these reasons, this variant has been classified as Pathogenic. |