@article{4cbaa5953be84514b44e51e74de77f81,
title = "Specifications of the ACMG/AMP variant curation guidelines for myocilin: Recommendations from the clingen glaucoma expert panel",
abstract = "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.",
keywords = "genetic testing, juvenile open-angle glaucoma, MYOC, primary open-angle glaucoma, variant classification, variant curation expert panel, variant interpretation",
author = "Burdon, {Kathryn P.} and Patricia Graham and Johanna Hadler and Hulleman, {John D.} and Francesca Pasutto and Boese, {Erin A.} and Craig, {Jamie E.} and Fingert, {John H.} and Hewitt, {Alex W.} and Siggs, {Owen M.} and Kristina Whisenhunt and Young, {Terri L.} and Mackey, {David A.} and Andrew Dubowsky and Emmanuelle Souzeau",
note = "Funding Information: This study was funded by a National Health and Medical Research Council (NHMRC) of Australia Centre for Research Excellence grant (GNT1116360), Program Grant (GNT1150144), Practitioner Fellowships to J.E.C, D.A.M and A.W.H., The Hospital Research Foundation Early Career Fellowship to E.S, A Core Grant for Vision Research from the National Eye Institute/National Institutes of Health to the University of Wisconsin‐Madison (P30EY016665) and an Unrestricted Grant from Research to Prevent Blindness, Inc. to the UW‐Madison Department of Ophthalmology and Visual Sciences to T.L.Y. and K.N.W. The authors would like to acknowledge the support of the ClinGen Sequence Variant Interpretation and Ocular Clinical Domain Working Groups, especially Kristy Lee. Funding Information: This study was funded by a National Health and Medical Research Council (NHMRC) of Australia Centre for Research Excellence grant (GNT1116360), Program Grant (GNT1150144), Practitioner Fellowships to J.E.C, D.A.M and A.W.H., The Hospital Research Foundation Early Career Fellowship to E.S, A Core Grant for Vision Research from the National Eye Institute/National Institutes of Health to the University of Wisconsin-Madison (P30EY016665) and an Unrestricted Grant from Research to Prevent Blindness, Inc. to the UW-Madison Department of Ophthalmology and Visual Sciences to T.L.Y. and K.N.W. The authors would like to acknowledge the support of the ClinGen Sequence Variant Interpretation and Ocular Clinical Domain Working Groups, especially Kristy Lee. Publisher Copyright: {\textcopyright} 2022 The Authors. Human Mutation published by Wiley Periodicals LLC.",
year = "2022",
month = dec,
doi = "10.1002/humu.24482",
language = "English (US)",
volume = "43",
pages = "2170--2186",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "Wiley-Liss Inc.",
number = "12",
}