Fig. 2

Human PALB2 variants and their effect on HR. a Schematic representation of the PALB2 protein with variant positions indicated and categorized as either neutral (green), truncating (red), VUS (blue) and synthetic missense variant (purple). The amino acid numbers are shown to specify the evolutionarily conserved functional domains of PALB2. PALB2 regions involved in the interactions with BRCA1, BRCA2, RNF168, and RAD51 are indicated. b DR-GFP assay in Trp53^KO/Palb2^KO mES cells expressing human PALB2 variants (or an empty vector control, Ev). Cells were transfected with an I-SceI and mCherry co-expression vector. GFP expression was monitored by FACS. Data represent mean percentages (±SEM) of GFP-positive cells among the mCherry-positive cells relative to wild type (WT), which was set to 100%, from two independent experiments, except for p.L939W and p.G998E for which data from three independent experiments are presented. Variants/conditions are categorized by color as either wild type (WT, black), likely benign SNV (green), truncating variant (red), VUS (blue), synthetic missense variant (purple) or empty vector (Ev, gray). Ev1–5 refer to Ev controls from 5 different replicates. Source data are provided as a Source Data file.