Prenatal genomic sequencing: Navigating uncertainty

Abstract

Prenatal genomic sequencing is now routine for fetal structural anomalies. Prenatal genomic sequencing results inform medical decision-making and guide pre and postnatal management by identifying associated clinical features, allowing planning, coordination, and timely treatment and avoiding unnecessary additional diagnostic tests. However, clinical details are limited in the prenatal setting making diagnostic certainty more difficult. This leads to more frequent variants of uncertain significance (VUS) and accompanying questions of if and when to report VUS. We review current practices and recommendations on reporting VUS and include perspectives of parents. However, there are no clear recommendations for reporting uncertain prenatal results. With greater access to prenatal phenotypes from retrospective and prospective prenatal cases and postnatal cases with the same recurrent variant, there should be greater certainty of results and lower frequency of VUS over time.