Known unknowns
Sorting the known unknowns is difficult enough. Of the 26,375 BRCA1 and BRCA2 variants reported in the public BRCA Exchange over half have no clinical interpretation. In order for experts to assess each of the rare variants, they must be collected from testing centers into databases such as ClinVar and LOVD . The review process entails combining statistical and rules-based information in a bayesian likelihood framework. One such framework has been developed by the ENIGMA consortium \cite{Parsons_2019} to assign interpretations for 7,256 variants in BRCA1 and BRCA2. Predicting clinical impact of a variant remain difficult, even using challenge-assisted computational and statistical workflows to interpret variants based on clinical and genomic information, with the best predictors wrong for about one out of every five variants \cite{Cline_2019}.