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Abstract

We are grateful to Vivanti et al. for their interest in our work and would like to address some of the questions raised in their Correspondence. In our study 'Whole-genome sequencing in prenatally detected congenital malformation: prospective cohort study in clinical setting' 1 , we aimed to investigate the diagnostic yield of clinical whole-genome sequencing (WGS) in prenatally detected congenital malformations.In the Stockholm region, we offer WGS instead of exome sequencing (ES) to all patients with an indication for genome-wide analysis in an academic-clinical investigation protocol. Currently, we are striving to implement WGS in the routine diagnosis of prenatally detected congenital malformations. In our study, we aimed to evaluate the workflow of prenatal WGS, from the recruitment process to receiving the results. We included prenatal cases with different types of congenital malformation, including milder phenotypes, similar to a standard clinical setting in a fetal medicine unit. As the authors mentioned, the diagnostic yield of an analysis method depends on the severity of the phenotypes included; hence, the inclusion criteria will affect the diagnostic yield of a study. The diagnostic yield is also dependent on the method used. Because our study was conducted in a clinical setting, the cases were prescreened for chromosomal aberrations according to the standard clinical investigation workflow, and we focused on variants that were exonic or were predicted to cause splice variants. These two factors can explain why we did not detect variants that ES could not detect. However, we believe that the strength of WGS lies