Analyzing patient genetic data can be time-consuming, often requiring hours of work with no conclusive results—especially in complex and rare cases. Our study explores gene prioritization with Exomiser to improve variant analysis in a cohort of unsolved cases lacking relative data for variant segregation.

By benchmarking its accuracy, we confirmed its effectiveness in identifying causative variants, including novel discoveries. We further streamlined the analysis process by optimizing use of phenotype descriptions and summarizing prioritization result data across the cohort.

This semi-automated approach accelerates molecular diagnosis and provides a standardized method for analyzing variant data in complex and rare cases. (By Victoria Lillback, https://jmg.bmj.com/content/early/2025/03/05/jmg-2024-110212 )