Necessary Annotations

ANNOVAR Necessary annotations

TAPES need a number of annotations to give the best possible estimation of a variant pathogenicity. You can use the --acmg flag when annotating with TAPES to directly use them.

The necessary/recommended databases are the following:

Annotation Required	ACMG Classification Criteria
Gene reference annotation (Refseq, ENSEMBL or UCSC)	All
dbscSNV	PVS1
gnomad_genome and either gnomad_exome or exac	PS1
Clinvar (20151201 or above)	PS3 / PP5 / BP6
DbNSFP (30a or above)	PP3 /BP4
dbsnp or avsnp	PS4

If one or more these annotations are missing. Do not use the --acmg flag while sorting.
TAPES will prioritise the variant using as many annotation as possible but will obviously be less powerfull.

VEP Necessary annotations

TAPES processing of VEP annotated vcf relies heavily on dbNSFP annotations. RefSeq reference annotations are recommended for VEP annotated vcf processing.

Necessary dbNSFP annotations :

• Interpro (for domain annotation)
• for in-silico prediction:
  • SIFT
  • LRT
  • MutationTaster
  • MutationAssessor
  • FATHMM
  • fathmm-MKL
  • PROVEAN
  • MetaSVM and MetaLR
  • M-CAP
  • GenoCanyon
  • GERP++
  • Polyphen-2
• clinvar
• gnomad_exome or ExAC
• gnomad_genome
• dbscSNV