Interpretation of standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology

Sequencing technology has evolved rapidly with the advent of high-throughput next-generation sequencing (NGS). By adopting NGS, more and more ophthalmologists and medical institutions are now performing genetic testing for molecular diagnosis and genetic research in genetic ocular disorders.Genetic testing has gradually become an indispensable test item in the diagnosis and treatment of patients with monogenetic ocular diseases and has been accompanied by new challenges in sequence interpretation due to increased complexity.As we know, NGS can detect a large number of the genetic variation data.Without strict standards to distinguish pathogenic variation from many potential functional variations in the human genome, false positive judgments of causality may be accelerated, which may hind the application and promotion of genetic diagnosis in clinical diagnosis as well as the biological understanding of diseases.The American College of Medical Genetics and Genomics (ACMG) has developed guidances for the interpretation of sequence variants and the Chinese Branch of Genetic Counseling has organized some experts in the field of genetic compiled the Chinese version of the ACMG Standards and Guidelines, which is one of the reference bases to help us interpret genetic variation.This article interpreted the ACMG Standards and Guidelines in order to provide reference for Chinese ophthalmologists in the classification of genetic variation, determination of pathogenic variation, application in clinical diagnosis and related genetic research.

Hereditary eye disease; Genetic variation; Classification standard; Clinical guideline; Interpretation