GUIDELINE FOR VARIANT CLASSIFICATION

The ACMG classification system is used to classify sequence variants for mendelian diseases, regardless of whether variants were detected by Sanger sequencing or NGS (Next Generation Sequencing).

Variants are separated into 5 classes according to IARC recommendations (Plon et al. 2008): 

                                        class 1             benign                                                            

                                        class 2             likely benign                                                    

                                        class 3             variant of uncertain significance (VUS)             

                                        class 4             likely pathogenic                                             

                                        class 5             pathogenic                     
                                

The following 3 chapters are based on the literature mentioned below and provide a schematic overview of the ACMG classification system. For detailed information we recommend reading the complete publications.

Chapter 1 lists all ACMG-criteria supporting pathogenicity and chapter 2 lists all ACMG-criteria supporting benignity. In order to classify a sequence variant into one of the five classes, the corresponding criteria are combined according to the table in chapter 3.

Ellard et al. 2020, ACGS Best Practice Guidelines for Variant Classification 2020 / Abou Tayoun et al. 2018, Hum Mutat 39:1517 / Richards et al. 2015, Genet Med 17:405 / Jarvik et Browning 2016, AJHG 98:1077 / Plon et al. 2008, Hum Mutat 29:1282