Extended Data Fig. 6: ESC-based BRCA2 SGE map for key functional domains reveal strong concordance to AlphaMissense prediction.
From: Saturation genome editing-based clinical classification of BRCA2 variants
a–d, 3D structural plots derived from BRCA2 CTDB domain from Alphafold depicting the helical domain, OB1, OB2 and OB3. The color code of the 3D structure plot is derived from AlphaFold and correlated with the pLDDT score, a score to provide information about the confidence of the prediction of a specific residue, in particular regions with a pLDDT score <50 are coloured in orange, regions with a pLDDT score between 50 and 70 are coloured in yellow, regions with a pLDDT score between 70 and 90 are coloured in light blue, regions with a pLDDT score > 90 are coloured in blue. In MAVISP we used structures or portion of structures with a pLDDT score > 70. Sequence-function map displaying the concordance of functional and non-functional categorization of individual amino acid changes across (a) helical domain residues 2479-2668, (b) OB1 residues from 2682-2794, (c) OB2 residues from 2804-3054 and (d) OB3 domain residues from 3073-3167 of the BRCA2 CTDB domain. The first box represents ESC-based BRCA2 SGE dataset and their concordance with MAVISP saturation scan and Alpha-Missense prediction. The box colour signifies “functional (blue)”, “non-functional (red)”, and “uncertain (turquoise blue)” class. The wildtype amino acid is shown as a circle, while white boxes indicate excluded amino acids. The Y-axis denotes the alternative amino acid changes. The magnified image of the 3D ribbon plot depicts the position of amino acid residues where clusters of functional/non-functional SNVs are reported across individual domains.
