30. A cost-effective bioinformatics triage strategy for testing PMS2 using short-read next generation sequencing

Pathogenic variants in the DNA mismatch repair gene PMS2 account for 5-25% of Lynch Syndrome. High homology and gene conversion between PMS2 and the pseudogene PMS2CL have imposed a significant technical challenge for the detection of alterations in the 3′ exons of PMS2 by short-read next generation sequencing (NGS). Currently, a complex and expensive approach is deployed to analyze PMS2. Long-range PCR followed by either Sanger sequencing or NGS is required to detect sequence variants. Multiplex ligation-dependent probe amplification can detect copy number variants (CNVs) in the 3′ exons but requires long-range PCR and sequencing to differentiate the origin of the deletions.