Data sources

Internal annotations

Internal annotations are used by the pipeline for prioritisation, variant classification, quality control, and preliminary filtering. These are not visible to the user.

Data source	AION version hg19	AION version hg38	Citations
Repeat definition	RepeatMasker from UCSC 2020-02-20	RepeatMasker from UCSC 2022-10-18 (hg38)	RepeatMasker Jurka, J et al. 2005
Hotspot definition	v9 (based on Clinvar 20/11/2024)	v9 (based on Clinvar 20/11/2024)	Richards, Sue et al. 2015
NMD	v9 Based on ensGene.txt.gz 06-04-2014	v9	Torene, Rebecca I et al. 2024
Uniprot functional domains	UniProt Release 06/2020	Uniprot release Release 05/2023	https://www.uniprot.org/
Global frequent artifact blacklist	v2	v1 native hg38	-
Whitelist of variants to keep with high gnomad freq	v1	v1 liftover	-
PP2 gene list	v9 (based on Clinvar 20/11/2024)	v9 (based on Clinvar 20/11/2024)	Richards, Sue et al. 2015
BP1 gene list	v9 (based on Clinvar 20/11/2024)	v9 (based on Clinvar 20/11/2024)	Richards, Sue et al. 2015
PVS1 gene list	v9 (based on Clinvar 20/11/2024)	v9 (based on Clinvar 20/11/2024)	Richards, Sue et al. 2015
Coding region BED file	Based on hg19.ensGene.gtf.gz 10-01-2020 + Clinvar 20/11/2024	Based on MANE v1.3 + Clinvar 20/11/2024	Relevant for MANE: Morales, Joannella et al. 2022

Small variants annotations

Table with annotation sources.

Data source	Version hg19	Version hg38	Citations / link
VEP: effect, ENSP, HGVS, SIFT, Polyphen	111	111	McLaren W et al 2016
ClinVar	20/11/2024	20/11/2024	Landrum MJ et al 2018
gnomAD	2.1.1 4.1.0 (liftover)	3.1.2 4.1.0	gnomAD Chen, Siwei et al. 2024
dbscSNV	v1.1	v1.1	Jian X et al. 2014
PhyloP	USCS phyloP46	UCSC phyloP100	Pollard KS, et al 2009
PhastCons	USCS phastCons46	UCSC phastCons100	Siepel A, et al. 2005
AION Classification (circe predictions)	v1	lifted over v1	-
Refseq	Ensembl 111	-	RefSeq: NCBI Reference Sequence Database
Grantham scores	From paper	From paper	R. Grantham 1974
BLOSUM62	BLOSUM62	BLOSUM62	Henikoff, S, and J G Henikoff. 1992
Canonical transcript definition	v9 Based on gnomAD v2.1.1 + APPRIS 2022_02.v47	v9 (MANE Select v1.3 + MANE Clinical v1.3)	Rodríguez, José Manuel, et al. 2013 Relevant for MANE: Morales, Joannella et al. 2022

CNV annotation sources

Table with annotation sources.

Data source	Version hg19	Version hg38	Citations
AnnotSV	3.3.6	3.3.6	Geoffroy, Véronique et al. 2018
Exomiser data	2202	2202	Smedley, Damian et al. 2015
gnomAD-SV	v2.1 (20/08/2020)	v2.1 (20/08/2020) liftover	Collins, Ryan L et al. 2020
ExAC	v0.3.1	v0.3.1	Lek, Monkol et al. 2016
ClinVar	20/11/2024	20/11/2024	Landrum MJ, Lee JM, Benson M, et al. 2018
ClinGen	01/12/2024	01/12/2024	Rehm, Heidi L et al. 2015
dbVar	30/10/2023	30/10/2023	Lappalainen, Ilkka et al. 2013
DDD	09/2015 (v9.2)	09/2015 (v9.2)	Firth, Helen V et al. 2009
DGV	25/02/2020	25/02/2020	MacDonald, Jeffrey R et al. 2014
1000 genomes	21/05/2017	21/05/2017	1000 Genomes Project Consortium et al. 2015
Ira M. Hall’s lab	31/12/2018 Static paper https://www.biorxiv.org/content/10.1101/508515v1.supplementary-material (liftdown)	31/12/2018 Static paper https://www.biorxiv.org/content/10.1101/508515v1.supplementary-material	Abel, Haley J et al. 2020
Children’s Mercy Research Institute	Liftdown 2021-10-27 Static GitHub VCF file	2021-10-27 Static GitHub VCF file (in GRCh38)	Kirsche, Melanie et al. 2023
RefSeq	17/08/2020	17/08/2028	https://www.ncbi.nlm.nih.gov/refseq/
Ensembl	07/02/2014	04/06/2022	https://www.ensembl.org/index.html
Breakpoints	20/03/2009	23/01/2014	Perez, Gerardo et al. 2024
Repeats	20/02/2020	18/10/2022	http://genome.ucsc.edu/cgi-bin/hgTables
Segmental duplications	26/09/2011	14/10/2014
ENCODE blacklist	v2 (2018) wgEncodeDacMapabilityConsensusExcludable.bed.gz	v2 (2018) hg38.blacklist.bed.gz	https://github.com/Boyle-Lab/Blacklist/
GAP	15/10/2021	15/10/2021	http://genome.ucsc.edu/cgi-bin/hgTables
Cytoband	14/06/2009 (GRCh37)	28/10/2022 (GRCh38)	http://hgdownload.cse.ucsc.edu/goldenpath/hg19/database/cytoBand.txt.gz
TAD boundaries	15/04/2024	21/11/2017	https://www.encodeproject.org/
ACMG	Static paper (https://pubmed.ncbi.nlm.nih.gov/35802134/) v3.1 78 genes	Static paper (https://pubmed.ncbi.nlm.nih.gov/35802134/) v3.1 78 genes

Disease & symptom annotation sources

Table with annotation sources.

Data source	Version	Citations / link
HPO	Downloaded 02/05/2024	https://hpo.jax.org/
Mondo	Downloaded 02/05/2024	http://purl.obolibrary.org/obo/mondo.json https://mondo.monarchinitiative.org/
GenCC	Downloaded 02/05/2024	https://search.thegencc.org/
HGNC	Downloaded 02/05/2024	https://www.genenames.org/
DDG2P	Downloaded 02/05/2024	https://www.deciphergenomics.org/ddd/ddgenes
PanelApp	Downloaded 02/05/2024	https://panelapp.genomicsengland.co.uk/