P827: Expanded chromosomal microarray comprising screening for spinal muscular atrophy and monogenic diseases in prenatal diagnosis

conditions, where applicable variants are considered highly penetrant and cause moderate-to-severe, childhood-onset disorders.However, the interpretation of conditions meeting such criteria remains at the discretion of testing laboratories, resulting in subjectivity.In this study, we outline PreventionGenetics' approach to evaluating genes included as an opt-in reporting category on fetal ES-hereafter, referred to as childhood onset disorders secondary findings (COD SF)-based on our interpretation of the ACMG recommendations.Methods: A preliminary list of genes for COD SF consideration was derived from PreventionGenetics' Clinicome, an internally curated list of genes with evidence for disease association (n= 6,237).To reduce subjectivity, the COD SF gene list inclusion was based on dual application of the predefined ACMG published criteria and a calculated gene score.Internal interpretation of the COD SF criteria was drafted, approved, and applied to genes by four reviewers.Gene scores were assigned based on ClinGen and GenCC gene-disease validity (points: 1-3), presence on specific expert-curated panels (points: 1-3), and clinical actionability evidence (points: 1).Genes selected for final inclusion had to satisfy all COD SF criteria and achieve a gene score of 3 or greater.Results: After filtering the Clinicome list by the internally defined COD SF criteria and applicable gene score, the final COD SF gene list included over 3000 genes, encompassing a wide variety of childhood-onset genetic conditions, including those associated with neurodevelopmental disorders, metabolic conditions, congenital anomalies, and other phenotypes. Conclusion:The option to report COD SF via fetal ES allows for consideration of conditions which may not be selected for reporting based solely on observed fetal presentation.Therefore, in the absence of a professionally predefined COD SF gene list, it remains critical for laboratories to maintain a well-curated, upto-date gene list for evaluation.From provider and patient perspectives, such a list will allow for appropriate pre-test counseling, informed decision making, and implementation of pregnancy care decisions2,3.From a laboratory perspective, a COD SF list is anticipated to decrease reporting variability and increase data review efficiency.Taken together, there is a strong argument for optional reporting of COD SF identified via fetal ES; however, care must be taken to ensure diagnostic (pathogenic/likely pathogenic) variants selected for reporting confer a reasonable risk of early-onset disease as outlined in the ACMG statement.In this study, we have described our process for COD SF gene list curation and encourage genetics professional societies to publish further guidelines to promote reporting consistency across laboratories.