Advancing Perinatal Genomic Discoveries through Patient Engagement and Data Sharing

/Abstract Fetal anomalies are observed in ~2-4% of pregnancies resulting in referral for genetic counseling and consideration of genetic testing. Although diagnostic yields for fetal anomalies have improved, substantial barriers to identifying genomic diagnoses exist and uncertainty remains regarding which results are appropriate to disclose prenatally. Genomic and health data sharing has resulted in rapid improvements in our understanding of postnatal gene-disease relationships and variant pathogenicity; similar efforts are needed to advance our understanding of prenatal genetic diagnosis. Here, we bring together leaders from ClinGen’s GenomeConnect and the Repository of the International Fetal Genomics Consortium (RIFGC), an expanding effort that aggregates and standardizes genomic and prenatal phenotype data from laboratories, clinicians, and researchers. Together, we will provide tools for patients to longitudinally engage with their genomic data through education and bidirectional data sharing including the opportunity to receive result updates through the work of ClinGen expert panels examining gene-disease validity and variant pathogenicity. Our overarching goal is to enable the translation of genomic data into precision medicine for patients undergoing diagnostic fetal sequencing (ES/GS) and to foster ongoing engagement. This goal addresses the NHGRI’s Notice of Special Interest in Development and Implementation of Clinical Informatics Tools to Enhance Patients’ Use of Genomic Information (NOT-HG-22-011). We will achieve our goals through the following aims: Aim 1: Engage participants who have had fetal sequencing to develop a patient and health record-driven registry focused on the longitudinal collection and sharing of genomic and phenotype data. Aim 2: Utilize participant-provided data to define gene-disease relationships, variant classification, and natural history of disorders identified via fetal sequencing, enabling participants to receive updated health information longitudinally. Aim 3: Evaluate parental experiences and preferences for fetal sequencing reanalysis practices and result return to inform study-related procedures and broader practices. Project Number: 1R01HG013710-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Human Genome Research Institute (NHGRI) | Principal Investigator: Erin Riggs (+1 co-PI) | Institution: GEISINGER CLINIC, DANVILLE, PA | Award Amount: $754,561 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 SEIR-B (80)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11132779