Journal article
Expert specification of the ACMG/AMP variant interpretation guidelines for genetic hearing loss
Human mutation, Vol.39(11), pp.1593-1613
11/2018
DOI: 10.1002/humu.23630
PMCID: PMC6188673
PMID: 30311386
Abstract
Due to the high genetic heterogeneity of hearing loss (HL), current clinical testing includes sequencing large numbers of genes, which often yields a significant number of novel variants. Therefore, the standardization of variant interpretation is crucial to provide consistent and accurate diagnoses. The Hearing Loss Variant Curation Expert Panel was created within the Clinical Genome Resource to provide expert guidance for standardized genomic interpretation in the context of HL. As one of its major tasks, our Expert Panel has adapted the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for the interpretation of sequence variants in HL genes. Here, we provide a comprehensive illustration of the newly specified ACMG/AMP HL rules. Three rules remained unchanged, four rules were removed, and the remaining 21 rules were specified. These rules were further validated and refined using a pilot set of 51 variants assessed by curators and disease experts. Of the 51 variants evaluated in the pilot, 37% (19/51) changed category based upon application of the expert panel specified rules and/or aggregation of evidence across laboratories. These HL-specific ACMG/AMP rules will help standardize variant interpretation, ultimately leading to better care for individuals with HL.
Details
- Title: Subtitle
- Expert specification of the ACMG/AMP variant interpretation guidelines for genetic hearing loss
- Creators
- Andrea M Oza - Boston Children's HospitalMarina T DiStefano - Harvard UniversitySarah E Hemphill - Mass General BrighamBrandon J Cushman - Mass General BrighamAndrew R Grant - Mass General BrighamRebecca K Siegert - Mass General BrighamJun Shen - Brigham and Women's HospitalAlex Chapin - ARUP LaboratoriesNicole J Boczek - Mayo ClinicLisa A Schimmenti - Mayo ClinicJaclyn B Murry - Mass General BrighamLinda Hasadsri - Mayo ClinicKiyomitsu Nara - Tokyo Medical CenterMargaret Kenna - Boston Children's HospitalKevin T Booth - University of IowaHela Azaiez - University of IowaAndrew Griffith - National Institute on Deafness and Other Communication DisordersKaren B Avraham - Tel Aviv UniversityHannie Kremer - Radboud University NijmegenHeidi L Rehm - Broad InstituteSami S Amr - Brigham and Women's HospitalAhmad N Abou Tayoun - University of PennsylvaniaClinGen Hearing Loss Clinical Domain Working Group
- Resource Type
- Journal article
- Publication Details
- Human mutation, Vol.39(11), pp.1593-1613
- DOI
- 10.1002/humu.23630
- PMID
- 30311386
- PMCID
- PMC6188673
- ISSN
- 1059-7794
- eISSN
- 1098-1004
- Grant note
- U41 HG006834 / NHGRI NIH HHS
- Language
- English
- Date published
- 11/2018
- Academic Unit
- Otolaryngology
- Record Identifier
- 9984383298802771
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