Fig. 6: Summary of DDX41 variant curation based on modified ACMG/AMP criteria.
From: Refinement of the classification of DDX41 variants through analysis of aggregated clinical datasets
Each of the 438 variants is shown on the x-axis (using abbreviated nomenclature), including start-loss (n = 4), frameshift (n = 67), nonsense (n = 38), canonical splice site (n = 37), intronic (n = 17), synonymous (n = 6), missense (n = 66) or in-frame (n = 3) pathogenic/likely pathogenic (P/LP), and missense (n = 190) or in-frame (n = 10) variants of uncertain significance (VUS). Twelve variants were excluded: structural (n = 6), untranslated region (n = 1), and missing variant information (n = 5 missense variants). The applicable ACMG/AMP criteria are shown in each row, including the comparison between two PP4 approaches (modified from Maierhofer et al. [3]. [PP4(original)] versus odds of pathogenicity from multinomial probability [PP4(OddsPath)]) and PP3/BP4 approaches (REVEL [PP3/BP4(revel)] versus AlphaMissense [PP3/BP4(alpha)]). The asterisks (*) on PS4 indicate the revised strength of evidence based on matching for East Asian genetic ancestry. Comparisons are made between the original and updated pathogenicity classifications, with red and blue text indicating upgraded and downgraded variants, respectively. Note that five variants have two different HGVSc descriptions (listed from left to right in the order of appearance) and are shown twice: R53fs (c.155dup, c.156_157insA); M316fs (c.947_948del, c.946_947del); T529fs (c.1585dup, c.1586_1587del); G72R (c.214G>A, c.214G>C); and M155I (c.465G>C, c.465G>A).
