Variant prioritisation

Question 1

What are the 2 methods of filtering a VCF file?

Answer 1

1. annotation based- Intronic variants, 5’ UTR and variants above a certain AF e.g. 1%
2. Quality based- Using QUAL scores (Alignment score) or depth criteria (DP)

Question 2

What are the 4 steps in variant prioritisation?

Answer 2

1. Filtering variants <1% in population frequency databases (gnomAD and 100 genomes project)
2. Prioritise based on functionality-
   High priority- Stop loss/gain, non-synonymous AA changes
   Low priority- Synonymous AA changes
3. Prioritise variants that have been previously associated with the disease phenotype of the referred patient (OMIM)
4. Selection of variants in combination with other information such as Pubmed and in-silico tool analysis