Table 2 Summarize the proposed recommendations for the use of PS4 in this study

Rule

Rule Description: The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls

PS4

PS4_OR: RR or OR, as obtained from case–control studies, is > 6.0 and the confidence interval around the estimate of RR or OR does not include 1.0

PS4_Moderate

PS4_OR: RR or OR, as obtained from case–control studies, is > 3.0 and the confidence interval around the estimate of RR or OR does not include 1.0; or

PS4_AC: allele count ≥ 6 in probands with variant absent in controls

PS4_Supporting

PS4_OR: OR or RR, as obtained from case–control studies, is > 2.27 with variants had an AF < 0.0005 in cases; or PS4_AC: allele count ≥ 3 in probands with variant absent in controls