AnnotSV

AnnotSV annotates and prioritizes structural variations (SVs) by integrating genomic, regulatory, and clinical annotations to assess SV pathogenicity.

Key Features:

• Integrated annotation: Compiles functionally, regulatory, and clinically relevant information including heterozygous and homozygous counts of single nucleotide variations (SNVs) and small insertions/deletions (indels) within each SV for analyzed patients.
• Allelic frequency computation: Reports computed allelic frequencies relative to overlapping variants from the Database of Genomic Variants (DGV).
• Large-source integration: Integrates annotations from over 20 sources, including genes, haploinsufficiency, triplosensitivity, regulatory elements, known pathogenic or benign genomic regions, and phenotypic data.
• Efficient processing benchmark: Demonstrated annotation of 4,751 SVs from a single 1000 Genomes Project sample while integrating information from four million SNVs/indels in less than 60 seconds.
• Prioritization module: Implements an ACMG/ClinGen-compliant scoring system that ranks SVs into five classes from pathogenic to benign.

Scientific Applications:

• Clinical variant interpretation: Supports identification and classification of human pathogenic SVs for diagnostic assessment.
• Genomic research: Facilitates investigation of SV contributions to genetic diversity, disease pathogenesis, and genotype–phenotype correlations.
• High-throughput studies: Enables large-scale annotation and prioritization of SVs in population and cohort sequencing projects such as the 1000 Genomes Project.

Methodology:

Compiles multi-source genomic annotations, computes allelic frequencies relative to DGV, integrates SNV/indel counts within each SV, and applies an ACMG/ClinGen-compliant prioritization module to classify SVs into five pathogenicity classes.