Overview of Specifications to the ACMG/AMP Variant Interpretation Guidelines

Curr Protoc Hum Genet. 2019 Sep;103(1):e93. doi: 10.1002/cphg.93.


The 2015 ACMG/AMP guidelines established a classification system for sequence variants; however, the broad scope of these guidelines necessitates specification of evidence types for specific genes or diseases of interest. Since publication of the guidelines, both general use and disease-focused specifications have emerged to aid in accurate application of ACMG/AMP evidence types. This article summarizes the approaches to, and rationale for, specifying three evidence categories (population frequency data, variant type and location, and case-level data), including available resources and a quantitative framework that can inform the specification process. © 2019 by John Wiley & Sons, Inc.

Keywords: ACMG/AMP guidelines; clinical genetics; variant interpretation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • American Medical Association
  • Data Interpretation, Statistical
  • Evidence-Based Practice
  • Gene Frequency
  • Genetic Diseases, Inborn / classification
  • Genetic Diseases, Inborn / genetics*
  • Genetic Predisposition to Disease / classification
  • Genetic Variation / genetics*
  • Genetics, Medical
  • Genetics, Population
  • Genome, Human / genetics*
  • Guidelines as Topic*
  • Humans
  • Pathology, Molecular
  • Societies, Medical
  • United States