Table 4 Heterogeneity analysis by bioinformatic groups

From: Classification of variants of uncertain significance in BRCA1 and BRCA2 using personal and family history of cancer from individuals in a large hereditary cancer multigene panel testing cohort

 Previous estimatesaThis study: P+VLP+VUSThis study: VLP+VUS
Bioinformatic groupNVAREstimate95% CINVAREstimate95% CINVAREstimate95% CI
Missense variants11770.120.08–0.1720320.130.10–0.1720070.090.06–0.13
 Not in key domain8540.00.0–0.0415070.0190.0–0.0515060.0080.0–0.05
 In key domain3230.350.26–0.455250.440.35–0.535010.360.26–0.44
 C02420.010.0–0.062770.230.11–0.352770.230.11–0.35
 C15–C25580.290.09–0.56730.420.17–0.68720.400.15–0.65
 C35–C55550.660.34–0.93480.510.23–0.79430.380.07–0.69
 C65980.810.61–0.951270.760.59–0.921090.590.28–0.90
Potential splice variants         
 High damage to wild type940.970.82–1.001080.910.77–1.0670.770.52–1.0
 Moderate damage to wild type660.340.15–0.55490.790.54–1.0400.610.27–0.95
 Increased de novo donor80.640.06–0.98260.140.0–0.43250.00.0–0.32
 Moderate de novo donor70.300.0–0.88480.150.0–0.40480.150.0–0.40
 All de novo donor15NANA740.140.0–0.33730.080.0–0.26
  1. CI confidence interval, NVAR number of variants, P pathogenic variant, VLP likely pathogenic variant, VUS variant of unknown significance.
  2. aEaston et al.,2 Tavtigian et al.,3 Vallee et al.5