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  5. Specifications of the ACMG/AMP variant curation guidelines for hereditary hemorrhagic telangiectasia genes—ENG and ACVRL1
 
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Specifications of the ACMG/AMP variant curation guidelines for hereditary hemorrhagic telangiectasia genes—ENG and ACVRL1
File(s)
3043736.pdf (769.92 KB)
Published version
Author(s)
DeMille, Desiree
McDonald, Jamie
Bernabeu, Carmelo
Racher, Hilary
Olivieri, Carla
more
Type
Journal Article
Abstract
The 2015 ACMG/AMP standards and guidelines for interpretation of sequence variants are widely used by laboratories, including for variant curation of the hereditary hemorrhagic telangiectasia (HHT) genes. However, the need for gene- and disease-specific modifications and specifications of these general guidelines to optimize and standardize variant classification was recognized at the time of publication. With this goal, the ClinGen HHT variant curation expert panel was formed. Here, we describe our recommended HHT-specific variant classification criteria and the outcomes from pilot testing of 30 variants of the ENG and ACVRL1 genes. Eight of the original ACMG/AMP rules were determined to not be applicable for ENG- or ACVRL1-related HHT or were previously recommended by ClinGen for removal, two rules were unmodified, and the remaining 18 rules were modified according to HHT specifications or previous ClinGen general recommendations. This study demonstrates the importance of HHT-specific criteria in the optimization and standardization of HHT variant classification and conflicting classification resolution.
Editor(s)
Scott, Stuart
Date Issued
2024-05-18
Date Acceptance
2024-04-24
Citation
Human Mutation, 2024, 2024, pp.1-13
URI
http://hdl.handle.net/10044/1/111892
URL
http://dx.doi.org/10.1155/2024/3043736
DOI
https://www.dx.doi.org/10.1155/2024/3043736
ISSN
1059-7794
Publisher
Wiley
Start Page
1
End Page
13
Journal / Book Title
Human Mutation
Volume
2024
Copyright Statement
Copyright © 2024 Desiree DeMille et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
License URL
Attribution 4.0 International
Identifier
http://dx.doi.org/10.1155/2024/3043736
Publication Status
Published
Article Number
3043736
Date Publish Online
2024-05-18
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