New ACMG Guidelines

Recently the American College of Medical Genetics published new guidelines for the interpretation of genetic sequence variants (Richards et al. (2015) Genetics in Medicine: Official Journal of the American College Of Medical Genetics: (PMID: 25741868). The process of variant interpretation is dynamic and challenging. The purpose of the guidelines is to standardize the terminology used by clinical laboratories when describing variants, and to establish specific criteria that should be utilized when interpreting sequencing variants. On Wednesday, September 30, 2015, GeneDx transitioned to using the new ACMG terminology in our reports. The chart below outlines the new terminology as it relates to our previous report language. Additionally, over the next 6 months, GeneDx will be implementing the guidelines into our variant interpretations. Please continue to check our website for updated information and announcements as we move forward with the implementation of these new guidelines.

Previous GeneDx Terminology New Terminology Based on ACMG Guidelines
Mutation Pathogenic variant
Variant, likely mutation/variant, likely disease-causing/expected pathogenic Likely pathogenic variant
Variant of unknown significance Variant of uncertain significance
Variant, likely benign Likely benign variant
Benign polymorphism Benign variant


Likely benign Variants

Variants that are interpreted to be “likely benign” have multiple lines of evidence supporting the argument that they are not the cause of disease in an individual. Therefore, in accordance with the ACMG guidelines, as of Thursday, October 29, 2015, GeneDx will no longer routinely report likely benign variants in our reports. A list of benign and likely benign variants can be provided upon request.