Variant Detection in 3′ Exons of PMS2 Using Exome Sequencing Data

• Published in: The Journal of molecular diagnostics : JMD Vol. 26; no. 9; pp. 843 - 850
• Main Authors: Mistry, Nipun A., Roellinger, Samantha E., Manninen, Matthew C., Gandham, Mallika, Koganti, Tejaswi, Balan, Jagadheshwar, Basu, Shubham, Blake, Emily J., Tandale, Pratyush P., Holdren, Megan A., Hoenig, Megan F., Urban, Rhianna M., Veith, Rebecca L., Kendzior, Matthew C., Wang, Chen, Gupta, Sounak, Shen, Wei
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2024
• ISSN: 1525-1578; 1943-7811; 1943-7811
• DOI: 10.1016/j.jmoldx.2024.06.001

PMS2 is one of the DNA-mismatch repair genes included in routine genetic testing for Lynch syndrome and colorectal, ovarian, and endometrial cancers. PMS2 is also included in the American College of Medical Genetics and Genomics' List of Secondary Findings Genes in the context of clinical exome and genome sequencing. However, sequencing of PMS2 by short-read–based next-generation sequencing technologies is complicated by the presence of the pseudogene PMS2CL, and is often supplemented by long-range–based approaches, such as long-range PCR or long-read–based next-generation sequencing, which increases the complexity and cost. This article describes a bioinformatics homology triage workflow that can eliminate the need for long-read–based testing for PMS2 in the vast majority of patients undergoing exome sequencing, thus simplifying PMS2 testing and reducing the associated cost.