Congenital anomalies occur in approximately 3% of all pregnancies and are a leading cause of perinatal, infant,
and childhood mortality and morbidity. The majority of these anomalies are identified during pregnancy but
despite the introduction of increasingly more sophisticated prenatal genomic testing such as sequencing, a
specific diagnosis is hampered by our inability to accurately interpret genomic data. A leading barrier to
interpretation is the lack of expert consensus regarding gene-disease association, variant pathogenicity, and
actionability of findings, creating challenges for obstetric and genetic providers to offer appropriate care.
Accordingly, in response to the Eunice Kennedy Shriver National institute of Child Health and Human
Development's interest in the genomics of birth defects, this application is a proposal to become a participating
ClinGen expert panel to evaluate the clinical relevance of genes and variants related to fetal congenital
anomalies. Our proposal will develop gene disease validity and variant curation expert panels to evaluate two
common and unique severe fetal disorders: non-immune fetal hydrops and unexplained stillbirth.
The variant and gene curation panels are composed of experts in clinical genetics, maternal fetal medicine,
molecular laboratory testing, computer science, developmental biology, genetic counseling and biocuration.
Members of our expert panel come from diverse national and international institutions and have extensive
experience in prenatal phenotyping and genotyping. The panel also has members who have served on other
ClinGen expert panels and committees, which will facilitate our integration into the ClinGen infrastructure.
Our proposal describes the details of our intended use of ClinGen policies, procedures, and tools to best
determine the clinical relevance of specific genes and variants to clinical care. We are committed to sharing our
data and results with others and contributing to the genetic knowledge base in the area of early developmental