Fig. 2

Prioritization of variants. A A case of proband with a single-exon deletion in the NF1 gene [35]. The deletion results in δ(g) = 0.8 for NF1. To calculate semantic similarity Φ(Q,D) for NF1, SvAnna evaluates five computational disease models associated with variants in NF1. In case of this proband, Neurofibromatosis, Type I (OMIM:162200) is the disease model that matches the proband’s clinical condition the best (Φ(Q,D) = 5.28). As NF1 is the only gene affected by the deletion, δ(g) and Φ(Q,D) of NF1 are the only determinants of the final PSV score. B A case of proband with an inversion involving 3′ end of CPNE9 and 5′ end of BRPF1 [36]. SvAnna assigns δ(g) score of 1 to both CPNE9 and BRPF1 that are disrupted by the inversion. Unlike the case of NF1 variant, the inversion involves > 1 genes; therefore, the final PSV integrates the scores of phenotypically relevant BRPF1 (8.25) and disrupted, but phenotypically non-relevant CPNE9 (1.00)