AnnotSV Manual Version 3.0.7 AnnotSV is a program for annotating and ranking structural variations from genomes of several organisms. This README version is dedicated to the human genome. https://lbgi.fr/AnnotSV/ Copyright (C) 2017-2021 GEOFFROY Véronique Please feel free to contact me for any suggestions or bug reports email: [email protected] AnnotSV documentation 2021/04/26 1 LEXIQUE 1000g: 1000 Genomes Project (phase 3) ACMG: American College of Medical Genetics and Genomics BED: Browser Extensible Data bp: base pair CDS: CoDing Sequence CNV: Copy Number Variation DDD: Deciphering Developmental Disorders DECIPHER: DatabasE of genomic varIation and Phenotype in Humans using Ensembl Resources DEL: Deletion DGV: Database of Genomic Variants DNA: DesoxyriboNucleic Acid DUP: Duplication ENCODE: Encyclopedia of DNA Elements ExAC: Exome Aggregation Consortium GH: GeneHancer GRCh37: Genome Reference Consortium Human Build 37 GRCh38: Genome Reference Consortium Human Build 38 HI: Haploinsufficiency hom: homozygous htz: heterozygous ID: Identifier indel: Insertion/deletion INS: Insertion INV: Inversion LoF: Loss of Function MCNV: multiallelic CNV MEI: Mobile Element Insertion misZ = Z scoreindicating gene intolerance to missense variation NAHR: Non-Allelic Homologous Recombination OMIM: Online Mendelian Inheritance in Man pLI: score indicating gene intolerance to a loss of function variation SNV: Single Nucleotide Variation SV: Structural Variations synZ = Z score indicating gene intolerance to synonymous variation TAD: Topologically Associating Domains Tcl: Tool Command Language TS: Triplosensitivity Tx: transcript VCF: Variant Call Format AnnotSV documentation 2021/04/26 2 TABLE OF CONTENTS 1. INTRODUCTION ............................................................................................................................................... 5 a) Overview ..................................................................................................................................................... 5 b) Supported organisms .................................................................................................................................. 6 2. INSTALLATION/REQUIREMENTS ..................................................................................................................... 6 a) Tcl (required) ............................................................................................................................................... 6 b) bedtools (required) ..................................................................................................................................... 6 c) Bcftools (required) ...................................................................................................................................... 6 d) Java (optional) ............................................................................................................................................. 7 e) AnnotSV source code (required) ................................................................................................................. 7 f) Filesystem Hierarchy Standard (FHS) .......................................................................................................... 8 3. ANNOTATION SOURCES .................................................................................................................................. 8 a) Gene annotations ........................................................................................................................................ 9 b) Regulatory Elements annotations ............................................................................................................. 10 c) Gene-based annotations ........................................................................................................................... 12 DDD gene annotations .................................................................................................................................. 12 OMIM annotations ........................................................................................................................................ 13 ACMG annotations ........................................................................................................................................ 13 Gene intolerance annotations (gnomAD) ..................................................................................................... 14 Gene intolerance annotations (ExAC) ........................................................................................................... 14 Haploinsufficiency annotations (DDD) .......................................................................................................... 15 Haploinsufficiency and triplosensitivity Scores annotations (ClinGen) ........................................................ 16 Phenotype-driven analysis powered by Exomiser ........................................................................................ 16 d) Known pathogenic genes or genomic regions annotation ....................................................................... 18 ClinVar pathogenic SV annotations ............................................................................................................... 18 Dosage sensitive genes/regions annotation (ClinGen) ................................................................................. 19 dbVarNR pathogenic SV annotations ............................................................................................................ 19 OMIM morbid genes ..................................................................................................................................... 20 e) Known pathogenic SNV/indel annotations ............................................................................................... 20 f) Known benign genes or genomic regions annotation .............................................................................. 21 gnomAD benign SV annotations ................................................................................................................... 22 ClinVar benign SV annotations ...................................................................................................................... 22 Not dosage sensitive genes/regions annotation (ClinGen) .......................................................................... 23 DGV benign SV annotations .......................................................................................................................... 23 DDD benign SV annotations .......................................................................................................................... 24 1000 genomes benign SV annotations.......................................................................................................... 24 Ira M. Hall’s lab benign SV annotations ........................................................................................................ 25 g) Breakpoints annotations ........................................................................................................................... 25 GC content annotations ................................................................................................................................ 25 Repeated sequences annotations ................................................................................................................. 26 Segmental duplication annotations .............................................................................................................. 27 ENCODE blacklist annotations ...................................................................................................................... 27 GAP annotations ........................................................................................................................................... 28 h) TAD boundaries annotations .................................................................................................................... 29 i) COSMIC annotations (not distributed)...................................................................................................... 30 4. VERSIONS OF THE ANNOTATION SOURCES .................................................................................................. 30 5. SV RANKING/CLASSIFICATION ....................................................................................................................... 31 6. SV TYPE .......................................................................................................................................................... 32 7. INPUT ............................................................................................................................................................ 32 a) SV input file (required) .............................................................................................................................. 33 AnnotSV documentation 2021/04/26 3 b) SNV/indel input files - for DELETION filtering (optional) .......................................................................... 34 c) Filtered SNV/indel input files - for compound heterozygosity analysis (optional) ................................... 35 d) External BED annotation files (optional) ................................................................................................... 35 e) External gene annotation files (optional)