Advanced PVS1 rule
Several check points is present in the current variant interpretation form for the evaluation of the importance of nonsense variants and setting ACMG tag PVS1. Evaluate if some of these can be implemented as REQs in a more advanced rule for PVS1. See related issues for each point.
Current check list:
- Is the premature stop codon located such that nonsense-mediated decay can be activated (>=50 bp upstream of last intron)? Related: #22
- Have LOF variants been reported in the same exon? (HGMD/gnomAD, use genome browser)
- Is haploinsufficiency (AD)/LOF (AR) known to be pathogenic in the gene? Related: #21 (closed)
- Have LOF variants been reported in gnomAD (heterozygous/homozygous for AD, homozygous for AR, hemizygous for X-linked)? (use genome browser)
- Are there known alternative transcripts that are unaffected by the variant? Related: LA-610
- Are there known alternative transcripts that are affected by the variant, but that are likely to cause a different phenotype? (use VEP results + external resources if worse CSQ found)
Related
- Consider this with the more general notion of null variants in the last part of a gene, #15 (closed)
- Evaluate if LOF prediction tools could be an option, e.g. LOFtool
- Better presentation of ACMG codes and REQs; #86 - could be used for a combination of manual and automatic checks
Edited by Morten C. Eike