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Table 1 Validation of mutational burden findings in autism genes

From: Calculating the statistical significance of rare variants causal for Mendelian and complex disorders

  Number of indivs with variant  
Gene LOF / de novo Nonsyn / de novo Inh / LOF P P including inh vars
ADCY5 0 2 1 0.723 0.446
ADNP 2 0 1 1.1 × 10 −3 1.7 × 10 − 3
CHD8 8 1 0 1.7 × 10−21 1.7 × 10− 21
DYRK1A 3 0 1 5.9 × 10−6 1.1 × 10−5
GRIN2B 3 1 0 8.2 × 10−5 8.2 × 10− 5
LAMC3 0 2 4 0.550 0.022
PTEN 1 2 1 8.2 × 10 −3 9.2 × 10 − 3
SBF1 0 2 1 0.833 0.502
SETD2 1 1 2 0.078 0.0110
SGSM3 0 2 2 0.086 0.0471
TBL1XR1 1 1 0 0.0167 0.0167
TBR1 2 1 0 3.4 × 10 −5 3.4 × 10 −5
UBE3C 0 2 1 0.432 0.291
  1. In a targeted sequencing study of 44 candidate autism genes in 2446 individuals [26], 12 genes contained both recurring de novo variants and inherited LOF variants in multiple individuals, or had evidence of excess mutation burden of de novo variants. Gene names that are in bold were statistically significant in the original study. P-values calculated using our methods validate findings by O’Roak et al. [27] for all 6 of these genes, and one additional gene. If we also consider inherited LOF variants, 3 additional genes are statistically significant using our methods. Inherited nonsynonymous variants were not reported in the original study, hence the P-value is conservative. Abbreviations: nonsyn nonsynonymous variant or single amino acid deletion, LOF loss-of-function variant, Inh inherited