Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000708120 | SCV000837230 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-11-23 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 1-6 of the MSH2 gene, which includes the initiator codon. If EPCAM has been tested and no copy number events are reported for it, then the 5' boundary of this event lies between the EPCAM and MSH2 genes. If EPCAM has not been tested, the 5' end of this event is unknown as it extends beyond the assayed region of this test. The 3' boundary is likely confined to intron 6 of the MSH2 gene. This gross deletion is expected to result in an absent or disrupted protein product. Deletions of exons 1-6 have been reported in several affected individuals and families, and are clearly defined as Lynch syndrome causative alleles (PMID: 15942939, 16086322, 16143124). A particular deletion of exons 1-6 of the MSH2 gene is a known founder mutation in the North American population (PMID: 12658575, 16143124, 14871915). Because the exact breakpoints of this deletion are unknown, it is uncertain whether or not the deletion identified in this individual is that founder mutation. ClinVar contains an entry for this variant (Variation ID: 254090). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic. |