CADD scores for SNVs and INDELs

[pbiology]

Combined Annotation Dependent Depletion (CADD)

• CADD is a tool for scoring the deleteriousness of single nucleotide variants as well as insertion/deletions variants in the human genome.
• CADD can quantitatively prioritize functional, deleterious, and disease causal variants across a wide range of functional categories, effect sizes and genetic architectures and can be used prioritize causal variation in both research and clinical settings. CADD has been described in three publications
• CADD has been described in three publications
  • Rentzsch P, Schubach M, Shendure J, Kircher M. CADD-Splice—improving genome-wide variant effect prediction using deep learning-derived splice scores. Genome Med. 2021 Feb 22. doi: 10.1186/s13073-021-00835-9. PubMed PMID: 33618777.
  • Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 2018 Oct 29. doi: 10.1093/nar/gky1016. PubMed PMID: 30371827.
  • Kircher M, Witten DM, Jain P, O'Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014 Feb 2. doi: 10.1038/ng.2892. PubMed PMID: 24487276.

Suggestion to add CADD to BALSAMIC is briefly mentioned in two BALSAMIC issues Add CADD scores to VCF for use in filtering in Scout #1100 and Dynamic CADD calculation for INDELs #834.

It will be a three step process, (Only step 2 is mentioned in the two issues linked above)

1. CADD for SNV
2. CADD for INDELs
3. CADD for SVs (if decided)

Can be closed when

• [x] #1126
• [x] #1150
• [x] Added CADD for INDELs, blocked by #1160
• [x] https://github.com/Clinical-Genomics/BALSAMIC/pull/1238

[pbiology]

Let's not also forget that the scout implementetion needs to happen!