Cystic fibrosis carrier screening in Australia: comparing sequencing and targeted panels across diverse ancestries.

Abstract

Targeted cystic fibrosis (CF) carrier screening panels may lack sensitivity in non-European ancestry groups. This study aims to evaluate the sensitivity of various panels in Australian CF carriers identified through sequencing. The following panels were evaluated in 869 CF carriers: Asuragen, Elucigene, Devyser, American College of Medical Genetics and Genomics and Victorian Clinical Genetics Services. Ancestry-specific CF carrier frequencies from population databases and Bayesian analysis were used to estimate post-test residual carrier risks. When variants with varying clinical consequences (VCC) were not considered, mean test sensitivity was highest in the Northern Europe group (95.6%) and lowest in the Southern Asia group (64.0%). The post-test residual carrier risk in the Northern Europe group was approximately 1 in 546, with only the Southern Asia group having a higher residual carrier risk of 1 in 179. The Southern Asia group exhibited the lowest test sensitivity and the highest post-test residual carrier risk, surpassing that of the Northern Europe group. The inclusion or exclusion of VCC significantly impacted the calculated test sensitivities. Further research is suggested to better characterise <i>CFTR</i> variants in non-European ancestry groups and to determine which VCC, if any, should be included in carrier screening reports.