nicoleruiz
commented
7 years ago We have added the following terms: SO:0002169 splice_polypyrimidine_tract_variant SO:0002170 splice_donor_region_variant
The definitions are the same as the ones you proposed. We made splice_donor_region_variant a child of splice_region_variant since the definition includes the 3rd and 6th base after the splice junction.
Let us know if these terms and their placement in the ontology work for you.
Nicole
From Sarah Hunt (seh@ebi.ac.uk):
Matt Hurles group at Sanger have been looking into the impact of variants on splicing and observed:
that there is some heterogeniety within the canonical splice sites; the donor +5 site is under stronger purifying selection and is more enriched for pathogenic mutations than all other non-canonical splice sites variation at the donor +2 site is typically less damaging than the other 3 canonical splice sites.
that the polypyrimidine stretch flanking the acceptor site extends beyond the ‘splice_region’ window and that mutations from pyrimidine to purine are more damaging than other changes.
They requested we annotate these regions more precisely in VEP. We discussed the suggestion on a VATT call and there was broad concensus this would be useful. We already have the term 'splice_donor_5th_base_variant', so would like to propose 2 additional terms:
splice_polypyrimidine_tract_variant Definition: variant falls in polypyrimidine tract at 3' end of intron, between the 17 and 3 bases from the end (acceptor -3 to acceptor -17) Parent: splicing_variant
splice_donor_region_variant Definition: variant falls in the region between the 3rd and 6th base after splice junction (5' end of intron) Parent: splice_site_variant
These are draft suggestions, of course - any improvements would be welcome! It might make sense to make splice_donor_5th_base_variant an child of splice_donor_region_variant, but I don't know if it's too disruptive to introduce new parents. What do you think?