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Table 2 Frequencies of NMDpositive variants in hereditary cancer, primary ciliary dyskinesia (PCD), and arrhythmia/cardiomyopathy genes in ExAC

From: Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation

   Variant allele frequencies in ExAC:
Gene Inheritance <0.005% 0.005–0.01% 0.01–0.05% 0.05–0.1% ≥0.1%
Hereditary cancer
APC Dominant 6 - - - -
ATM Recessive 104 1 - - -
BARD1 Dominant 22 - - - -
BLM Recessive 38 2 1 - -
BMPR1A Dominant 3 1 - - -
BRCA1 Dominant 67 - 2 - -
BRCA2 Dominant 103 2 1 - -
BRIP1 Recessive 32 - 1 - -
CDH1 Dominant 5 - - - -
CDKN2A Dominant 4 - - - -
CHEK2 Dominant 29 3 2 - 1
CTRC Dominant 11 1 - - -
EPCAM Recessive 9 1 - - -
FANCC Recessive 23 1 - - -
MEN1 Dominant - - - - -
MLH1 Dominant 5 - - - -
MRE11A Recessive 18 1 - - -
MSH2 Dominant 7 1 - - -
MSH6 Dominant 25 - 1 - -
MUTY Recessive 19 3 2 - 1
NBN Recessive 33 1 1 - -
NF1 Dominant 23 1 - - -
PALB2 Dominant 35 2 1 - -
PMS2 Dominant 32 - - - -
PTCH1 Dominant 2 - - - -
PTEN Dominant 2 - - - -
RAD50 Recessive 42 2 3 - -
RAD51C Recessive 19 3 - - -
SMAD4 Dominant 2 - - - -
SPINK1 Dominant 1 - 1 - -
STK11 Dominant - - - - -
TP53 Dominant 1 - - - -
VHL Dominant - - - - -
Primary ciliary dyskinesia
ARMC4 Recessive 36 3 - - -
C21orf59 Recessive 7 1 1 - -
CCDC103 Recessive 3 - - - -
CCDC114 Recessive 6 - - - -
CCDC151 Recessive 16 1 - - -
CCDC39 Recessive 22 2 - - -
CCDC40 Recessive 32 1 1 - -
CCDC65 Recessive 17 - 1 - -
CCNO Recessive - - - - -
DNAAF1 Recessive 19 2 1 - -
DNAAF2 Recessive 12 - - - -
DNAAF3 Recessive 16 2 1 - -
DNAH11 Recessive 80 1 2 - -
DNAH5 Recessive 113 - 2 - -
DNAI1 Recessive 15 - 1 - -
DNAI2 Recessive 21 1 1 - -
DNAL1 Recessive 3 - - - -
DRC1 Recessive 22 - 2 - -
DYX1C1 Recessive 18 1 - - -
RPGR Recessive 1 - - - -
RSPH1 Recessive 9 1 2 - -
RSPH4A Recessive 27 1 - - -
RSPH9 Recessive 4 - - - -
SPAG1 Recessive 21 2 - - -
ZMYND10 Recessive 16 - - - -
Arrhythmia and cardiomyopathy
BAG3 Dominant 2 - - - -
CACNA1C Dominant 6 - - - -
CASQ2 Recessive 15 - - - -
DES Recessive 5 - - - -
DSC2 Dominant 13 - - - -
DSG2 Dominant 19 - - - -
DSP Recessive 21 - - - -
FHL1 Dominant - - - - -
HCN4 Dominant 5 - - - -
JUP Recessive 7 - - - -
KCNE1 Dominant - - - - -
KCNH2 Dominant 5 - 2 - -
KCNQ1 Dominant 15 - 1 - -
LAMP2 Dominant - - - - -
LMNA Dominant 1 - - - -
MYBPC3 Dominant 17 - - - -
NKX2-5 Dominant 1 - - - -
PKP2 Dominant 18 - 1 - -
PLN Dominant - - - - -
SCN5A Dominant 9 - - - -
TRDN Recessive 6 1 2 - -
  1. All NMDpositive variants for genes associated with hereditary cancer, primary ciliary dyskinesia, and arrhythmia/cardiomyopathy were binned based on their allele frequencies in the ExAC dataset. In all genes listed, loss of protein function has been established as the mechanism of disease. Several of the genes listed are associated with both dominant and recessive inheritance patterns; the listed inheritance patterns are specifically for those associated with the disorders most relevant to the clinical area, and the mechanism of disease is loss of function. For example, BRCA2 is associated with autosomal dominant hereditary breast and ovarian cancer, as well as autosomal recessive Fanconi anemia. DES and DSP genes are associated with both dominant and recessive arrhythmia and cardiomyopathy disorders. However, the loss-of-function mechanism has only been firmly established with the recessive disorders