Table 2

Illustration of the “variants reduction” pipeline on the Ogden syndrome data set and the synthetic Miller syndrome data set

Data setOgden (exome variants in hg19 coordinate)Miller (genome variants in hg18 coordinate)
Variants reduction strategyDefaultCustomDefaultCustomCustom
Input variants14791479470218747021874702187
Identify missense, nonsense and splicing variants136136124101241012410
Identify variants from conserved regions5395
Remove variants in segmental duplications regions5135
Remove variants observed in user-supplied controls16*
Remove variants observed in the 1000 Genomes Project with MAF>1%193227511162275
Remove variants observed in the NHLBI-ESP 5400 exomes with MAF>1%14312567401256
Remove variants in dbSNP (excluding clinically associated SNPs)11516313516
Remove variants with SIFT score >0.051395
Remove variants with PolyPhen2 score <0.851351
Final list of candidate genes based on disease model11241014
Correct causal gene identified?YesYesYesYesNo
  • * Two unaffected male family members were used as controls.

  • SNP, single nucleotide polymorphism.