Figure 2.

Evidence for CYP24A1 c.823T>C; p.(Trp275Arg) variant classification. The ACMG utilises a series of evidence criteria in support of a pathogenic (P) or benign (B) classification. The different types of evidence (functional, genetic, population, in-silico etc) are stratified according to the level of evidence (supporting, moderate, strong or very strong) and a pathogenicity classification (pathogenic, likely pathogenic, variant of unknown significance (VUS), likely benign or benign) assigned according to a set of ‘combined criteria’ provided in the guidelines (19). PM, moderate evidence of pathogenicity; PP, supporting evidence of pathogenicity. The level of evidence is then categorised numerically: PM1, located in functional domain; PM2, absent from controls; PM3, recessive disorder and present in trans with a pathogenic mutation; PP4, functional biochemical evidence; PP3, in silico evidence supporting pathogenicity.