Skip to main content

Table 1 Summary of the negative clinical WES cases and genetic findings. For a full list of cases including negative and previously published, please refer to Additional file 5: Table S4. The symbol “a” indicates a novel gene (no assigned OMIM phenotype) for condition to be reported elsewhere

From: Analysis of transcript-deleterious variants in Mendelian disorders: implications for RNA-based diagnostics

ID

Phenotype

Gene

Mutation HGVS nomenclature

Zygosity

Type of mutation

Class of transcript-deleterious variants

Notes

17DG0527

Global developmental delay, hypotonia, epilepsy, postnatal microcephaly, strabismus and choreoathetosis

a

 

Homozygous

Frameshift indel

 

Novel gene for this condition

15DG1507

Epilepsy and global developmental delay

a

 

Homozygous

Transcript-deleterious variant

c

Novel gene for this condition

18DG0320

Multiple congenital anomalies

a

 

Homozygous

Missense

 

Novel gene for this condition

18DG0989

Neonatal adrenoleukodystrphy

a

 

Homozygous

Missense

 

Novel gene for this condition

19DG0509

Undefined epileptic encephalopathy

a

 

Homozygous

Nonsense

 

Novel gene for this condition

18DG0669

Microcephaly, atrial septal defect, ventricular septal defect

a

 

Homozygous

Transcript-deleterious variant

a

Novel gene for this condition

17DG0738

Chronic interstitial kidney disease with small kidneys

a

 

Homozygous

Nonsense

 

Novel gene for this condition

19DG0230

Griscelli syndrome

a

 

Homozygous

Missense

 

Unpublished

17DG0872

Hydrocephalus, agenesis of corpus callosum, macrocephaly

a

 

Homozygous

Transcript-deleterious variant

b

Novel gene for this condition

17DG1071

Cholestasis, progressive familial intrahepatic 3

ABCB4

NM_000443.3:c.286+335A>G:p.(Val96Glyfs*11)

Homozygous

Transcript-deleterious variant

c

Unpublished

16DG0145

Intellectual disability

ADAT3

NM_138422.1:c.382G>A:p. (Val128Met)

Homozygous

Missense

 

Unpublished

16DG1223

Oligohydramios, short long bones and echogenic kidneys

ANKS3

NM_133450:c.352G>A:p.(Ala118Thr)

Homozygous

Missense

 

PMID:27417436

18DG0295

Joubert syndrome

ARL3

NM_004311.3:c.445C>T:p.(Arg149Cys)

Homozygous

Missense

 

PMID: 30269812

15DG2104

Joubert Syndrome

ARMC9

NM_025139.3:c.51+5G>T:p.?, r.1_51del

Homozygous

Transcript-deleterious variant

c

PMID: 27431290

15DG2485

Asparagine synthetase deficiency

ASNS

NM_133436.2:c.28A>C:p.(Ser10Arg)

Homozygous

Missense

 

PMID:30214071

15DG0357

Bardet-Biedl syndrome

BBS1

NM_024649.4:r. [1232_3423del]

Homozygous

Large deletion

 

PMID: 27894351

16DG1620

Osteopetrosis

CLCN7

NM_001287.5:c.739-18G>A;(p.Met250Argfs*6)

Homozygous

Transcript-deleterious variant

c

PMID: 29620724

19DG1262

Multiple congenital anomalies

COG6

NM_020751.2:c.695-8T>G

Homozygous

Transcript-deleterious variant

c

Unpublished

PSMMC0118

Short stature on growth hormone replacement, subclinical hypothyroidism, grade 1 hydronephrosis (Lt), delayed bone age, IVF pregnancy, first of a twin, delayed development

CREBRF

NM_001168393.2:c.475delT;p.(Ser159Hisfs*57)

Heterozygous

Frameshift indel

 

PMID: 31130284

17DG0967

Cholestasis with high GGT and renal failure

DCDC2

NM_001195610.1:c.223_293del:p.(Arg75Leufs*16)

Homozygous

Frameshift indel

 

Unpublished

17DG0996

Cholestasis

DCDC2

NM_001195610.1:c.223_293del:p.(Arg75Leufs*16)

Homozygous

Frameshift indel

 

Unpublished

13DG2237

Warsaw breakage syndrome

DDX11

NM_004399.2: c.2426T>G:p. (Val809Gly)

Homozygous

Missense

 

PMID: 30214071

17DG0022

Chronic unexplained diarrhea

DGAT1

NM_012079.5:c.836T>C:p.(Leu279Pro)

Homozygous

Missense

 

Unpublished

16DG0357

Acromesomelia

DIP2C

NM_014974.2:c.3283C>T:p.(Arg1095Trp)

Homozygous

Missense

 

PMID:29620724

17DG0756

Congenital disorder of glycosylation

FUT8

NM_178155.2:c.943C>T:p.(Arg315*)

Homozygous

Nonsense

 

PMID: 30237576

16DG0733

Severe progressive microcephaly, global developmental delay and epilepsy

GPR56

NM_005682.5:c.1503C>A;p.(Tyr501*)

Homozygous

Nonsense

 

PMID: 27431290

PSMMC0115

Unexplained macrocephaly, epilepsy, short stature and developmental delay

KCND1

NM_004979.6:c.1883G>A:p.(Arg628Lys)

Hemizygous

Missense

 

Unpublished

15DG2234

Microcephaly, cerebral white matter abnormality and intellectual disability

KCTD3

NM_016121.3 c.1036_1073del:p.(P346Tfs*4)

Homozygous

Transcript-deleterious variant

d

Unpublished

13DG2107

Psychomotor retardation and seizures

KCTD3

NM_016121.3 c.1036_1073del:p.(P346Tfs*4)

Homozygous

Transcript-deleterious variant

d

PMID:25558065

17DG0404

High GGT neonatal cholestasis/sclerosing cholangitis

KIF12

NM_138424.1:c.610G>A:p.(Val204Met)

Homozygous

Missense

 

PMID: 30250217

18DG0966

Methylmalonic aciduria and homocystinuria

LMBRD1

NM_018368.4:c.1156C>T:p.(Arg386*)

Homozygous

Nonsense

 

Unpublished

16DG0559

Joubert syndrome

LRRC34

NM_001172779:c.199A>T:p.(Lys67*)

Homozygous

Nonsense

 

In press

17DG0731

Disseminated tuberculosis, hypogammaglobulinemia, nearly all T and B cells are naive

MAP3K14/NIK

NM_003954.3:c.916delT: p.(Cys306Valfs*2)

Homozygous

Frameshift indel

 

doi.org/10.1016/j.jaci.2018.11.003

15DG2492

Short stature, global developmental delay, dysmorphism, congenital heart disease , PUJ obstruction and partial agenesis of corpus callosum

MFSD11

NM_001242532.1:c.143G>C:p.(Gly48Ala)

Homozygous

Missense

 

PMID: 28940097

16DG0621

Severe neurodevelopmental disorder

MICU2

NM_152726.3:c.42G>A:p.(Trp14*)

Homozygous

Nonsense

 

PMID: 29053821

17DG1094

Megacystis

MYH11

NM_022844.2:c.1033+1G>A

Homozygous

Transcript-deleterious variant

a

PMID: 30237576

12DG2078

Klippel-Feil syndrome and myopathy

MYO18B

NM_032608.5:c.6905C A:p.(Ser2302*)

Homozygous

Nonsense

 

PMID:25748484

18DG0176

Microcephaly, developmental delay, visual impairment, hyponatremia, failure to thrive, choreoathetoid movement, seizures

NUP214

NM_005085:c.461:p.(Asp154Gly)

Homozygous

Missense

 

PMID:30758658

16DG1424

Diarrhea, failure to thrive, intestinal failure and TPN dependence

PERCC1

Deletion of regulatory element (chr16:1480850_1483950del)

Homozygous

Transcript-deleterious variant

f

Unpublished

18DG0670

Erythrokeratoderma

PERP

NM_022121.4:c.466G>A:p.(Gly156Arg)

Homozygous

Missense

 

PMID: 31898316

16DG1048

Peroxisome biogenesis disorder 12A (Zellweger)

PEX19

NM_001193644.1:c.161C>T:p. (Ser54Leu)

Homozygous

Missense

 

PMID: 30561787

13DG0810

Congenital Microcephaly

PPFIBP1

NM_001198915.1:c.960_961del:p.(Glu320Aspfs*3

Homozygous

Frameshift indel

 

PMID: 30214071

16DG0201

Short stature, brachydactyly, intellectual disability and seizures

PRMT7

NM_019023.2:c. 190C>T:P. (Gln64*)

Homozygous

Nonsense

 

PMID: 28940097

15DG2427

Syndromic cataract

RIC1

NM_020829.3: c.3794G>C:p.(Arg1265Pro)

Homozygous

Transcript-deleterious variant

b

PMID: 27878435

13DG1181

Primary microcephaly

RTTN

NM_173630.3:c.5746-20A>G:p.1917_1942del

Homozygous

Transcript-deleterious variant

c

PMID: 30214071

17DG1005

Bardet-Biedl syndrome

SCLT1

NM_144643.2:c.290+2T>C:p.(Lys79Valfs*4)

Homozygous

Transcript-deleterious variant

a

PMID: 30237576

16DG0760

Epilepsy, generalized, with febrile seizures plus, type 1

SCN1B

NM_001037.3:c.355T>G:p.(Tyr119Asp)

Homozygous

Missense

 

PMID: 28218389

PSMMC0210

Hypotonia, global developmental delay, cardiac disease, leukodystophy

SCN3A

NM_001081676.1:c.1485T>G:p.(Ser495Arg)

Heterozygous

Missense

 

Unpublished

18DG0278

Congenital insensitivity to pain

SCN9A

NM_002977.3:c.2311-14T>G

Homozygous

Transcript-deleterious variant

c

Unpublished

14DG0045

Renal failure, morbid obesity, intellectual disability, retinitis pigmentosa (sibling of 14DG0047, see Table S5)

SDCCAG8

NM_006642.2:c.741-152G>A, p.Arg247Serfs*23; NM_006642.2: r.740_741ins741-202_741-1

Homozygous

Transcript-deleterious variant

c

In press

16DG0276

Tricho-Hepato-Enteric Syndrome

SKIV2L

NM_006929.5:c.3561_3581del; p.(Ser1189_Leu1195del)

Homozygous

Non-frameshift indel

 

Unpublished

16DG0815

Tricho-Hepato-Enteric Syndrome

SKIV2L

NM_006929.5:c.3561_3581del; p.(Ser1189_Leu1195del)

Homozygous

Non-frameshift indel

 

Unpublished

17DG0977

Tricho-Hepato-Enteric Syndrome

SKIV2L

NM_006929.4:c.3561_3581del,p.(Ser1189_Leu1195del)

Homozygous

Non-frameshift indel

 

Unpublished

18DG0594

Pseudovaginal perineoscrotal hypospadias

SRD5A2

NM_000348:c.682G>A:p.(Ala228Thr)

Homozygous

Missense

 

Unpublished

17DG0821

Congenital adrenal hyperplasia (CAH)

STAR

NM_000349.2:c.201_202del:p.(Tyr68Glnfs*2)

Homozygous

Frameshift indel

 

Unpublished

18DG0512

Osteogenesis imperfecta, type XIV

TMEM38B

NM_018112.2:c.455_542del;p.(Gly152Alafs*5)

Homozygous

Frameshift indel

 

Unpublished

16DG0114

Muscular dystrophy-dystroglycanopathy

TMEM5

NM_014254.3:c.686A>G:p.(Tyr229Cys)

Homozygous

Missense

 

Unpublished

16DG1117

Leukodystrophy

TRAK1

NM_001042646: c.287-2A>G

Homozygous

Transcript-deleterious variant

a

PMID:28940097

16DG0659

Muscular dystrophy, limb-girdle, autosomal recessive 18

TRAPPC11

NM_021942.6:c.464C>T:p.(Ser155Leu)

Homozygous

Missense

 

Unpublished

16DG1614

Global developmental delay and epilepsy

UFC1

NM_016406.3:c.317C>T:p. (Thr106Ile)

Homozygous

Missense

 

PMID: 29868776

16DG0018

Osteogenesis imperfecta

WNT3A

NM_033131.3:c.254G>A:p.(Arg85Gln)

Homozygous

Missense

 

PMID: 29620724

14DG0613

Primary microcephaly

YARS

NM_003680.3:c.789C>A:p.(Phe263Leu)

Homozygous

Missense

 

PMID: 28383543/30214071

15DG2661

Dysmorphism

ZFAT

NM_020863.3:c.1199G>A:p.(Arg400Gln)

Homozygous

Missense

 

PMID: 28640246/28940097