Estimating Yields of Prenatal Carrier Screening and Implications for Design of Expanded Carrier Screening Panels

Purpose: Prenatal genetic carrier screening can identify parents at risk of having a child affected by a recessive condition. However, the conditions/genes most appropriate for screening remain a matter of debate. Estimates of carrier rates across genes are needed to guide construction of carrier screening panels. Methods: We leveraged an exome sequencing database (n=123,136) to estimate carrier rates across 6 major ancestries for 416 genes associated with severe recessive conditions. Results: 36.5% (East Asian) to 65% (Ashkenazi Jewish) of individuals are variant carriers in at least one of the 416 genes. For couples, screening all 416 genes would identify 0.4-2.8% of couples as being at-risk for having a child affected by one of these conditions. Screening just the 47 genes with carrier rate > 1.0% would identify more than 85% of these at-risk couples. An ancestry-specific panel designed to capture genes with carrier rates > 1.0% would include 6 to 30 genes, while a comparable pan-ethnic panel would include 47 genes. Conclusion: Our work guides the design of carrier screening panels and provides data to assist in counseling prospective parents. Our results highlight a high cumulative carrier rate across genes, underscoring the need for careful selection of genes for screening.