Carrier screening: an update

• This study provides a comprehensive review of the literatures for carrier screening currently available. • The carrier frequency (CF) and at-risk couples (ARCs) rate for pathogenic variants of rare autosomal recessive disorders varies widely according to the population studied. Some studies utilized data-driven approach to interpret the criteria of a Tier 3 carrier screening based on CF threshold suggested by ACMG. • The severity or seriousness of genetic condition is a key factor for disorders inclusion criteria. ARCs for severe or profound disease were more likely to choose alternative reproductive options than those for moderate disease. The understanding of severity of genetic conditions of perspectives of couples with known family history, affected individuals, and so on, are increasingly acknowledged. • CS panel must have clinical validity at the level of gene‐disease association, laboratories can adapt ACMG-ClinGen technical standards for variants interpretation concordance. Variant classification is still a major challenge for carrier screening. • The residual risks (RR) to be a carrier or have an affected child for a specific condition is always present, and is not always quantifiable because unprecise disease prevalence, CF and detection rate (DR). Genetic carrier screening (CS) for reproductive decision making was introduced 50 years ago. Technological advances and improvements in knowledge of the human genome makes multi-disease, pan-ethnic CS possible. Such screening will identify most individuals as carriers of at least one autosomal recessive or X-linked recessive disorder. Past experiences and best practices have provided a framework for CS. Although its clinical utilization is increasing, some challenges remain. In this study, several aspects of CS panel implementation have been addressed including how to evaluate the quantitative gene inclusion criteria, how to classify the severity of genetic conditions, how to understand clinical validity at the level of gene–disease association and variant classification, and how to minimize residual risks.