Fig. 3: Comparison of BRCA2 MAVE data with data from functional assays and in silico predictors.
From: Functional evaluation and clinical classification of BRCA2 variants
a–d, Boxplots showing functional scores of SNVs encoding missense variants compared with a BRCA2–/– V-C8 HDR assay (a), a DLD1 BRCA2–/– olaparib sensitivity assay (b), a prime-editing-based haploid cell-survival assay (c) and a mouse Brca2–/– embryonic stem cell complementation assay (d). The numbers of variants of each type resulting from the individual assays are shown. Functionally abnormal variants have significantly lower functional scores than functionally normal variants in a (P = 1.6 × 10−52), b (P = 2.0 × 10−11), c (P = 3.4 × 10−8) and d (P = 1.1 × 10−4), using two-sided Mann–Whitney–Wilcoxon tests. P values for all comparisons are shown. Boxes represent the interquartile range, the horizontal line is the median functional score, and whiskers show maximum and minimum values. Variants are shown as points and coloured by the functional strength of the evidence category. e, Comparison of the AUC values between MAVE and two in silico predictors (AlphaMissense and BayesDel) using ClinVar-classified missense standards (n = 70). f, Comparison of the AUC values between MAVE and two in silico predictors (AlphaMissense and BayesDel) using missense variants characterized using a well-calibrated HDR assay (n = 417).
