Curating the Clinical Genome 2024 ePoster Gallery-Curating the Fetal Genome Experience of the ClinGen Prenatal Gene Curation Expert Panel

Curating the Fetal Genome Experience of the ClinGen Prenatal Gene Curation Expert Panel

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The document discusses the work of the ClinGen Prenatal Gene Curation Expert Panel in curating the fetal genome to improve the understanding of gene-disease relationships in prenatal genetic diagnosis. With the increasing use of genomic sequencing in prenatal testing, interpreting variants is challenging due to limited fetal phenotypic information. The panel focuses on genes associated with unique pregnancy-related phenotypes like non-immune fetal hydrops and stillbirth. They train curators on standardized scoring of genetic evidence and pair clinicians with biocurators for gene curation. The panel prioritizes genes based on prenatal uniqueness and reviews evidence in virtual meetings to establish causative gene-disease relationships. Since 2021, they have completed primary and secondary curation for genes linked to fetal anomalies, stillbirth, and non-immune fetal hydrops.<br /><br />The objective of the panel is to quantify evidence supporting genes linked to severe prenatal phenotypes like stillbirth and non-immune fetal hydrops. They have curated genes such as AMER1, CHRNG, and FLT4 among others, focusing on causality assignment for identified variants. The panel consists of members from 16 international institutions, including prenatal clinicians, biocurators, coordinators, and ClinGen staff, who collaborate to enhance knowledge about genetic diseases affecting pregnancies. Challenges in assigning pathogenicity to variants in prenatal genome-wide sequencing are addressed through collective clinical and scientific expertise. This collaborative effort aims to improve prenatal diagnosis accuracy and clinical counseling. The project is funded by the NIH under grant number 5 U24 HD104588.

Keywords

ClinGen Prenatal Gene Curation Expert Panel

fetal genome

gene-disease relationships

prenatal genetic diagnosis

genomic sequencing

fetal phenotypic information

unique pregnancy-related phenotypes

gene curation

evidence-based prioritization

prenatal diagnosis accuracy

Ignatia Van den Veyver (iveyver@bcm.edu)