ClinSV: Clinical grade structural and copy number variant detection from whole genome sequencing data

André E. Minoche; Ben Lundie; Greg B. Peters; Thomas Ohnesorg; Mark Pinese; David Morgan Thomas; Andreas Zankl; Tony Roscioli; Nicole Schönrock; Sarah Kummerfeld; Leslie Burnett; Marcel E. Dinger; Mark J. Cowley

doi:10.1186/s13073-021-00841-x

Genetic & Genomic MedicineGenome MedicineFeb 25, 2021

Peer-reviewed journal article

ClinSV: Clinical grade structural and copy number variant detection from whole genome sequencing data

André E. Minoche iD, Ben Lundie iD, Greg B. Peters iD, Thomas Ohnesorg iD, Mark Pinese iD, David Morgan Thomas iD, Andreas Zankl iD, Tony Roscioli iD, Nicole Schönrock, Sarah Kummerfeld iD, Leslie Burnett iD, Marcel E. Dinger iD, Mark J. Cowley iD

Abstract

Whole genome sequencing (WGS) has the potential to outperform clinical microarrays for the detection of structural variants (SV) including copy number variants (CNVs), but has been challenged by high false positive rates. Here we present ClinSV, a WGS based SV integration, annotation, prioritisation and visualisation method, which identified 99.8% of pathogenic ClinVar CNVs >10kb and 11/11 pathogenic variants from matched microarrays. The false positive rate was low (1.5-4.5%) and reproducibility high (95-99%). In clinical practice, ClinSV identified reportable variants in 22 of 485 patients (4.7%) of which 35-63% were not detectable by current clinical microarray designs.

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