期刊
HUMAN MUTATION
卷 43, 期 8, 页码 1097-1113出版社
WILEY-HINDAWI
DOI: 10.1002/humu.24302
关键词
Angelman syndrome; Christianson syndrome; guidelines; Pitt-Hopkins syndrome; Rett syndrome; variant interpretation
资金
- National Human Genome Research Institute of the National Institutes of Health (NIH) [U41HG006834]
- Victorian Government's Operational Infrastructure Support Program
- Royal Children's Hospital Foundation
The Rett and Angelman-like Disorders Variant Curation Expert Panel (Rett/AS VCEP) provided customized variant interpretation criteria for genes MECP2, CDKL5, FOXG1, UBE3A, SLC9A6, and TCF4, which led to high consistency in interpretation among multiple curators. 13 variants had classification changes when assessed using the modified guidelines.
The genes MECP2, CDKL5, FOXG1, UBE3A, SLC9A6, and TCF4 present unique challenges for current ACMG/AMP variant interpretation guidelines. To address those challenges, the Rett and Angelman-like Disorders Variant Curation Expert Panel (Rett/AS VCEP) drafted gene-specific modifications. A pilot study was conducted to test the clarity and accuracy of using the customized variant interpretation criteria. Multiple curators obtained the same interpretation for 78 out of the 87 variants (similar to 90%), indicating appropriate usage of the modified guidelines the majority of times by all the curators. The classification of 13 variants changed using these criteria specifications compared to when the variants were originally curated and as present in ClinVar. Many of these changes were due to internal data shared from laboratory members however some changes were because of changes in strength of criteria. There were no two-step classification changes and only 1 clinically relevant change (Likely pathogenic to VUS). The Rett/AS VCEP hopes that these gene-specific variant curation rules and the assertions provided help clinicians, clinical laboratories, and others interpret variants in these genes but also other fully penetrant, early-onset genes associated with rare disorders.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据