SVRare

SVRare aggregates and annotates rare structural variants from whole genome sequencing datasets to enable discovery and characterization of disease-causing structural variants.

Key Features:

• Aggregation of Structural Variants: Aggregates structural variant calls from multiple callers, including Manta and Canvas, into a unified dataset and applied this approach to the 100K Genomes Project data (554,060,126 structural variants across 71,408 participants).
• Efficient Annotation: Annotates rare structural variants to help distinguish potential disease-causing variants from a high background of false positives.
• Discovery of Novel Variants: Identified 36 novel protein-coding disrupting structural variants on diagnostic-grade genes in a pilot cohort of 4,313 families.
• Increased Diagnostic Yield: Estimated to increase structural variant–based diagnostic yield by at least fourfold.
• Genome-Wide Association Studies (GWAS): Facilitates GWAS of structural variants and has revealed clusters of disease-causing SVs in genes such as PKD1/2 and LDLR.

Scientific Applications:

• Rare disease variant discovery: Identification and prioritization of disease-causing structural variants in rare-disease cohorts.
• Clinical diagnostics: Increasing the detection rate of pathogenic structural variants in clinical genetics analyses.
• Gene-disease association studies: Enabling GWAS to detect gene-level associations involving structural variants, exemplified by PKD1/2 and LDLR.
• Large-scale WGS analysis: Processing and annotating population-scale whole genome sequencing datasets for variant discovery and interpretation.

Methodology:

Aggregates SV calls from callers including Manta and Canvas, performs annotation of rare structural variants, and supports genome-wide association studies; applied to whole genome sequencing data from the 100K Genomes Project (554,060,126 SVs, 71,408 participants) and a pilot of 4,313 families.