Fig. 4: Genomic data analysis workflow for the BabyScreen+ study.

^aKnown benign variants include those classified as benign or likely benign by the Victorian Clinical Genetics Services (VCGS) and/or submitted as such in national (Shariant³⁹) and/or international databases (for example, ClinVar, (likely) benign with at least two stars). ^bVery common variants include those with a frequency of more than 2% in VCGS internal data and/or the Genome Aggregation Database. ^cKnown pathogenic variants include those classified as (likely) pathogenic by VCGS, in national databases (Shariant³⁹) and/or international databases (ClinVar). ^dHigh-impact variants include nonsense, frameshift, canonical splice site, start loss, stop loss, and large deletions and duplications. ^eVariants in the literature include missense, in-frame and splice region variants in the Mastermind Cited Variant Reference (now known as the Indexed Variant File). ^fVariants too common for monoallelic disease (0.01% in Genome Aggregation Database) or biallelic disease (0.1% in Genome Aggregation Database). Mode of inheritance (MOI) is derived from the MOI of the gene in the BabyScreen+ panel in PanelApp Australia. ^gOnly heterozygous variants are allowed for monoallelic MOI. Biallelic MOI requires a homozygous or hemizygous zygosity, or else two (or more) variants in the same gene. VCF, variant call file.