as far as I know Polyphen2 (http://genetics.bwh.harvard.edu/pph2/) predicts variant effect based on 2 different DB:
- HumDiv: Mendelian disease variants vs. divergence from close mammalian homologs of human proteins (>=95% sequence identity).
- HumVar: all human variants associated with some disease (except cancer mutations) or loss of activity/function vs. common (minor allele frequency >1%) human polymorphism with no reported association with a disease of other effect.
...but I was wondering, looking at some exome results, how to deal with discrepancies?? Let's say: "possibly" in HumDiv and "benign" in HumVar, which one is more reliable to be disease-associated? I mean, a variant can not be damaging for a Mendelian disease but not associated to any other...or there is something I am missing?
Thanks a lot in advance for any help!!