RT Journal Article
SR Electronic
T1 Expert Specification of the ACMG/AMP Variant Interpretation Guidelines for Genetic Hearing Loss
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 313734
DO 10.1101/313734
A1 Andrea M. Oza
A1 Marina T. DiStefano
A1 Sarah E. Hemphill
A1 Brandon J. Cushman
A1 Andrew R. Grant
A1 Rebecca K. Siegert
A1 Jun Shen
A1 Alex Chapin
A1 Nicole J. Boczek
A1 Lisa A. Schimmenti
A1 Jaclyn B. Murry
A1 Linda Hasadsri
A1 Kiyomitsu Nara
A1 Margaret Kenna
A1 Kevin T. Booth
A1 Hela Azaiez
A1 Andrew Griffith
A1 Karen B. Avraham
A1 Hannie Kremer
A1 Heidi L. Rehm
A1 Sami S. Amr
A1 Ahmad N. Abou Tayoun
A1 ClinGen Hearing Loss Clinical Domain Working Group
YR 2018
UL http://biorxiv.org/content/early/2018/05/08/313734.abstract
AB Due to the high genetic heterogeneity of hearing loss, 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 hearing loss. 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) standards and guidelines for the interpretation of sequence variants in hearing loss genes. Here, we provide a comprehensive illustration of the newly specified ACMG/AMP hearing loss rules. Three rules remained unchanged, four rules were removed, and the remaining twenty-one rules were specified. Of the specified rules, four had general recommendations, seven were gene/disease considerations, seven had strength-level specifications, and three rules had both gene/disease and strength-level specifications. These rules were further validated and refined using a pilot set of 51 variants assessed by curators. These hearing loss-specific ACMG/AMP rules will help standardize variant interpretation, ultimately leading to better care for individuals with hearing loss.GRANT NUMBERS Research reported in this publication was supported by the National Human Genome Research Institute (NHGRI) under award number U41HG006834.