OC11.01: *Clinical experience with carrier screening in a general population: support for a comprehensive pan‐ethnic approach

To present next generation sequencing (NGS) based expanded carrier screening (CS) results from the USA. Single-gene disorder carrier status for 381,014 individuals was determined using NGS-based pan-ethnic CS for up to 274 genes. Detection rates were compared to literature derived values. Data for guideline-recommended (Ashkenazi Jewish [AJ] disorder panel) or commonly screened genetic disorders (cystic fibrosis, spinal muscular atrophy, fragile X) were further examined. After excluding at-risk spinal muscular atrophy and α-thalassemia silent carriers, combined theoretical at-risk couple and expected affected pregnancy rates for 274 disorders were calculated. Of all the genes screened, 117/274 (42.7%) had observed carrier rates significantly different from expected (figure 1). For AJ disorders, 81.6% (4,434/5,435) of carriers identified did not report AJ ancestry. For cystic fibrosis, 44.0% (6,260/14,229) of carriers identified had a variant not on the standard 23 mutation panel. At-risk silent spinal muscular atrophy carriers, undetectable by standard screening, were present in 1/39 (8,763/344,407) individuals. For fragile X, compared to standard premutation screening, AGG interruption analysis modified risk in 83.2% (1,128/1,356) of carriers. Assuming random pairing, 1/44 (2.3%) couples would be expected to be at-risk and 1/175 (0.6%) pregnancies would be affected by a disorder in the 274 gene screening panel. NGS-based CS provides increased identification of at-risk couples compared to standard screening. These data support offering NGS-based CS to all reproductive-aged women. Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.