University Of Tasmania
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Specifications of the ACMG/AMP variant curation guidelines for myocilin: Recommendations from the clingen glaucoma expert panel

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journal contribution
posted on 2023-05-21, 15:59 authored by Kathryn BurdonKathryn Burdon, Patricia GrahamPatricia Graham, Hadler, J, Hulleman, JD, Pasutto, F, Boese, EA, Craig, JE, Fingert, JH, Alexander HewittAlexander Hewitt, Siggs, OM, Whisenhunt, K, Young, TL, David MackeyDavid Mackey, Dubowsky, A, Souzeau, E
The standardization of variant curation criteria is essential for accurate interpretation of genetic results and clinical care of patients. The variant curation guidelines developed by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015 are widely used but are not gene specific. To address this issue, the Clinical Genome Resource (ClinGen) Variant Curation Expert Panels (VCEP) have been tasked with developing gene-specific variant curation guidelines. The Glaucoma VCEP was created to develop rule specifications for genes associated with primary glaucoma, including myocilin (MYOC), the most common cause of Mendelian glaucoma. Of the 28 ACMG/AMP criteria, the Glaucoma VCEP adapted 15 rules to MYOC and determined 13 rules not applicable. Key specifications included determining minor allele frequency thresholds, developing an approach to counting probands and segregations, and reviewing functional assays. The rules were piloted on 81 variants and led to a change in classification in 40% of those that were classified in ClinVar, with functional evidence influencing the classification of 18 variants. The standardized variant curation guidelines for MYOC provide a framework for the consistent application of the rules between laboratories, to improve MYOC genetic testing in the management of glaucoma.


National Health & Medical Research Council


Publication title

Human Mutation










Menzies Institute for Medical Research



Place of publication

Div John Wiley & Sons Inc, 605 Third Ave, New York, USA, Ny, 10158-0012

Rights statement

© 2022 The Authors. Human Mutation published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Repository Status

  • Open

Socio-economic Objectives

Diagnosis of human diseases and conditions