Summary

Genetic changes called structural variants (SVs) show up as deletions, duplications or rearranged pieces of DNA. Although they are less common than single- nucleotide variants, many SVs cause disease, so finding them is important for patient care. Standard genetic test tools often miss some SV types. We evaluated a “breakpoint” analysis method to see how often it finds clinically important SVs in targeted next-generation sequencing (NGS) panel tests. 

Methods:
More than 80,000 patient samples were tested using exome-based NGS panels. An in-house breakpoint method, combining read-pair and split-read signals, was used to detect deletions, tandem duplications, inversions, and retrotransposon element (RTE) insertions. Only rare SVs with potential clinical impact that were not detected by other callers were included. 

Key Findings:
The method identified 162 clinically relevant SVs (97 unique), affecting 0.2% of all panel orders and 0.3% of positive reports. Most were disease-causing or likely disease-causing, and many were RTE insertions or partial exon deletions. 

Conclusion:
Breakpoint analysis reveals important SVs that standard tools may miss, increasing diagnostic yield and helping explain previously unclear genetic test results.  

View the poster

Authors:

Lotta Koskinen, Margarita Andreevskaya, Antti Väisänen, Mikko Muona, Tuuli Pietilä, Janica Djupsjöbacka, Ville Kytölä, Kati Kämpjärvi, Pertteli Salmenperä, Juha Koskenvuo, Miko Valori