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

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, prioritization, and visualization framework, which identified 99.8% of simulated 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. ClinSV is available at https://github.com/KCCG/ClinSV.

Automated summary

ClinSV is a WGS-based framework for integration, annotation, prioritization, and visualization of structural variants with low false positive rates and high reproducibility. In clinical practice, ClinSV identified reportable variants that were undetectable by current clinical microarray designs in a significant percentage of cases.