Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000464824 | SCV000563993 | pathogenic | Lynch syndrome | 2016-09-05 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 6-9 of the EPCAM gene. The 5' boundary is likely confined to intron 5. The 3' end of this event is unknown, as it extends through the termination codon beyond the assayed region for this gene, but is likely confined to the intergenic space between the EPCAM gene and the MSH2 gene, as no copy number variations were detected in MSH2. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated EPCAM protein. 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). Similar deletions of EPCAM exons 6-9 have been reported in individuals and families affected with Lynch syndrome (PMID: 23801599, 19098912, 21309036, 19177550). For these reasons, this variant has been classified as Pathogenic. |