PharmVar Tutorial Standardises CYP2D6 Structural Variant Detection and Reporting
This PharmVar consortium tutorial provides comprehensive guidance on detecting and reporting the complex structural variation at the CYP2D6 locus, including gene deletions, duplications, and hybrid arrangements. It defines standardised terminology for clinical and research reporting that is essential for accurate genotype-to-phenotype translation. For molecular diagnostics laboratories offering CYP2D6 testing, the paper is an indispensable reference for assay validation, result interpretation, and EHR-compatible reporting.
The original study
PharmVar Tutorial on CYP2D6 Structural Variation Testing and Recommendations on Reporting.
- Authors
- Turner AJ, Nofziger C, Ramey BE, Ly RC, Bousman CA, Agúndez JAG, et al.
- Journal
- Clinical pharmacology and therapeutics
- Type
- Review, Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural
- PMID
- 37669183
Original abstract
The Pharmacogene Variation Consortium (PharmVar) provides nomenclature for the highly polymorphic human CYP2D6 gene locus and a comprehensive summary of structural variation. CYP2D6 contributes to the metabolism of numerous drugs and, thus, genetic variation in its gene impacts drug efficacy and safety. To accurately predict a patient's CYP2D6 phenotype, testing must include structural variants including gene deletions, duplications, hybrid genes, and combinations thereof. This tutorial offers a comprehensive overview of CYP2D6 structural variation, terms, and definitions, a review of methods suitable for their detection and characterization, and practical examples to address the lack of standards to describe CYP2D6 structural variants or any other pharmacogene. This PharmVar tutorial offers practical guidance on how to detect the many, often complex, structural variants, as well as recommends terms and definitions for clinical and research reporting. Uniform reporting is not only essential for electronic health record-keeping but also for accurate translation of a patient's genotype into phenotype which is typically utilized to guide drug therapy.