Fig. 2: Comparative results of the MANO-B method with the IARC, ClinVar, and Align-GVGD classifications for 107 variants.
From: High-throughput functional evaluation of BRCA2 variants of unknown significance
DLD1 BRCA2 (−/−) cells transfected separately with the 107 BRCA2 variants or the empty vector were treated with PARP inhibitors (olaparib, niraparib, and rucaparib), CBDCA, or DMSO at the indicated concentrations. The relative viability of the cells treated with each drug was calculated based on the viability of vehicle-treated cells, then normalized to that of cells expressing wild-type BRCA2. All variants were ordered by relative viability at the optimal concentration. The classification of the MANO-B method was based on the relative viability at the optimal concentration of each drug and defined as normal (relative viability of 1–82), intermediate (83–87), and abnormal (88–108). The IARC, ClinVar, and Align-GVGD classifications are color-coded in each column. The ClinVar classifications of five variants (V159E, M1168I, K1530N, G1696V, and A2911E) without assertion criteria were considered as VUSs.
