Table 1.

Quantification of BAP1 SGE assay performance in the classification of missense variants using the ACMG-AMP framework

Validation truth set	No. Path.	No. Ben.	Assay readout (pathogenics)		Assay readout (benigns)		LRPath	PS3	LRBen	BS3
			Dep.	U/E	Dep.	U/E
ClinVar (≥2*)	0	6	0	0	0	6	−	−	0	NA
ClinVar (≥1*)	7	6	7	0	0	6	6.0	PS3_mod	7.0	BS3_mod
Systematic	2,423	138	2,419	4	4	134	27.6	PS3_str	470.6	BS3_vstr

Assay performance was evaluated based on the relative numbers of depleted (Dep.) and unchanged/enriched (U/E) readouts observed for the truth sets of pathogenic (Path.) and benign (Ben.) variants. Truth sets were either constructed using all available ClinVar-classified missense variants with ≥2* review status or ≥1* review status or using a systematic approach in which the pathogenic truth set consisted of nonsense and frameshift variants and the benign truth set consisted of missense variants ascribed benignity based on current ACMG-AMP requirements (two evidence items toward benignity unless BA1 was met). ACMG, American College of Medical Genetics and Genomics; AMP, Association for Molecular Pathology; mod, moderate; str, strong; vstr, very strong; NA, not applicable.