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}.