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

Area of Science:

• Genetics
• Bioinformatics
• Cancer Genomics

Background:

• The PMS2 gene is crucial for DNA mismatch repair and is routinely tested for Lynch syndrome and various cancers.
• Sequencing PMS2 is challenging due to its pseudogene, PMS2CL, often requiring complex and expensive long-read methods.
• PMS2 is also part of the American College of Medical Genetics and Genomics' secondary findings gene list.

Purpose of the Study:

• To develop a bioinformatics workflow to streamline PMS2 sequencing.
• To eliminate the need for costly long-read based approaches for PMS2 analysis in exome sequencing.
• To reduce the complexity and cost associated with PMS2 genetic testing.

Main Methods:

• Development of a bioinformatics homology triage workflow.
• Utilizing short-read next-generation sequencing data.
• Implementing a computational approach to differentiate PMS2 from its pseudogene.

Main Results:

• The homology triage workflow successfully eliminates the need for long-read based testing for PMS2 in most cases.
• The method simplifies PMS2 analysis within broader exome sequencing.
• Significant reduction in complexity and cost for PMS2 genetic testing is achieved.

Conclusions:

• A bioinformatics homology triage workflow offers a cost-effective and simplified solution for PMS2 genetic testing.
• This approach enhances the efficiency of exome sequencing by removing the requirement for specialized long-read techniques for PMS2.
• The workflow facilitates routine genetic screening for Lynch syndrome and associated cancers.