Curating the Clinical Genome 2024 ePoster Gallery-RPGR Variant Curation Using Adapted ACMG

RPGR Variant Curation Using Adapted ACMG_AMP Guidelines

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The document discusses the adaptation of ACMG/AMP guidelines by the XLIRD VCEP for variant curation of the RPGR gene, which is responsible for X-linked Inherited Retinal Diseases (IRD). These guidelines are crucial due to the increasing demand for genetic diagnoses with emerging IRD gene therapies. By implementing ClinGen variant curation practices, evidence code specifications for RPGR variants were developed and tested on 50 pilot variants. Specific variants within RPGR were classified based on their impact on post-translational modification and protein length changes, with gene-specific adaptations allowing successful classification of 200 variants. These classifications will be published in ClinVar following approval. The systematic curation of RPGR variants has resolved conflicts and classified previously unclassified variants, contributing to the development of a template for variant curation of other genes associated with X-linked IRD. Funding for this work is provided by NIH awards and Janssen, with support from various organizations including ClinGen. The X-linked IRD VCEP thanks the ClinGen Retina Gene Curation Expert Panel and the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel for their contributions.

Keywords

ACMG/AMP guidelines

XLIRD VCEP

RPGR gene

X-linked Inherited Retinal Diseases

genetic diagnoses

ClinGen variant curation practices

post-translational modification

protein length changes

ClinVar

NIH awards