Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV001354413 | SCV001549026 | pathogenic | Lynch syndrome | no assertion criteria provided | clinical testing | The PMS2 c.164-?_2006+?del variant (chr:7 g.6026390_6043689del GRCh37) results in a deletion of exons 3-11, although the precise breakpoints of this deletion were not determined, nor were the effects of this variant on the resulting mRNA or protein product determined. The variant was not identified in the literature nor was it identified in dbSNP, GeneInsight-COGR, Cosmic, Zhejiang University Database, Mismatch Repair Genes Variant Database, or Insight Hereditary Tumors Database. The variant was identified in ClinVar (classified as pathogenic by Invitae). The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). The c.164-?_2006+?del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 55 and leads to a premature stop codon 19 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the PMS2 gene are an established mechanism of disease in PMS2 associated cancers and is the type of variant expected to cause the disorder. Further, this variant was identified by our laboratory in a patient with a PMS2-deficient tumour. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. |