Supplementary methods; FS1: BRIP1 nonsense and frameshift mutations; FS2: BRIP1 expression in CRISPR cell lines; FS3: hydroxyurea and TMPyP4 challenge; FS4: HEK293TN CRISPR cell lines; FS5: HeLa stable clone rescues; FS6: Transient rescue screening assay; FS7: Degradation of missense mutant proteins; TS1: List of BRIP1 missense variants identified in cohorts