Pathogenicity classification of germline gene variants related to disorders with Mendelian inheritance

Classification	Interpretation*
Pathogenic	Associated with disease risk
Likely pathogenic	>90% likelihood of disease risk association
Variant of uncertain significance (VUS)	Available data do not allow classification into one of the other categories
Likely benign	>90% likelihood that variant is not associated with disease risk
Benign	Not associated with disease risk

Criteria for pathogenicity are a continuum, and some laboratories may reach different conclusions regarding the pathogenicity of specific variants. The likelihood of disease in an individual depends on other factors besides pathogenicity of a specific variant, including the inheritance pattern of the disorder (dominant or recessive), other risk factors (genetic or acquired), and the disease penetrance in the population (likelihood that individuals with a pathogenic variant will develop disease).

* Based on a set of defined criteria including:

Population data (allele frequency; prevalence of variant in affected individuals versus controls)
Computational data (predicted effect on protein sequence or function)
Functional data (functional studies show or do not show deleterious effect)
Segregation data (variant segregates with disorder in families)

Adapted from: ACMG Laboratory Quality Assurance Committee. 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. Genet Med 2015; 17:405.

Graphic 122646 Version 6.0

خرید پکیج

Pathogenicity classification of germline gene variants related to disorders with Mendelian inheritance