New Genotypes and Phenotypes in Patients with 3 Subtypes of Waardenburg Syndrome Identified by Diagnostic Next-Generation Sequencing

Table 3

Summary of the new SNV results of the molecular screening of WS-related genes, including location of mutations, pathogenicity predictions, and population data.

Subject ID

WS type

Chromosome location

Gene

Mutation

Protein mutation

Pathogenicity prediction

Population frequency

Inheritance status

SIFT_pred

Polyphen2_HVAR_pred

Polyphen2_HDIV_pred

MutationTaster_pred

CADD13_PHRED

1000g_EAS

ExAC_EAS

esp6500si_all

49

2

Chr2(q36.1)

PAX3

c.808C>G

p.R270G

NA

D

NA.

D

32

—

—

—

Novel

51

2

Chr2(q36.1)

PAX3

c.117C>A

p.N39K

T

D

D

D

25.9

—

—

—

Novel

109

1

Chr2(q36.1)

PAX3

c.808C>G

p.R270G

D

D

B

D

32

—

—

—

Novel

112

1

Chr2(q36.1)

PAX3

c.152T>G

p.L51R

D

D

D

D

29.5

—

—

—

De novo

65,66

1

Chr2(q36.1)

PAX3

c.793-3T>G

NA

NA

NA

NA

D

12.22

—

—

—

Novel

113,114

1

Chr2(q36.1)

PAX3

c.803G>T

p.S268I

D

D

D

D

33

—

—

—

De novo

113,114

1

Chr2(q36.1)

PAX3

c.801delT

p. F267Lfs17

T

NA

P

NA

NA

—

—

—

De novo

7,8

2

Chr3(P13)

MITF

c.642_650delAAG

NA

NA

NA

NA

NA

NA

—

—

—

De novo

20

4

Chr22(q13.1)

SOX10

c.122G>T

p.G41V

T

B

B

D

15.9

0.0109

0.0082

0.000077

De novo

102

4

Chr22(q13.1)

SOX10

c.127C>T

p.R43X

D

NA

B

A

35

—

—

—

De novo

76

2

Chr22(q13.1)

SOX10

c.122G>T

p.G41V

D

B

D

D

15.9

0.0109

0.0082

0.000077

De novo

76

2

Chr8(q11..21)

SNAI2

c.230C>G

p. S77C

D

B

P

D

21.3

0.004

0.0045

—

De novo

17

2

Chr8(q11..21)

SNAI2

c.365C>T

p.A122V

D

P

D

D

25.2

0.001

0.0015

—

De novo

85

1

Chr13(q22..3)

EDNRB

c.481A>G

p.K161E

T

P

B

D

23.3

—

—

—

De novo

92

1

Chr13(q22..3)

EDNRB

c.1018C>G

p.H340D

D

D

D

D

32

—

—

—

De novo

111

1

Chr13(q22..3)

EDNRB

c.1015C>T

p.L339F

T

D

D

D

23.2

—

—

—

De novo

Novel refers to variants that were absent in 200 control subjects; de novo refers to variants that were absent in the parents and 200 control subjects. “NA” means “not applicable.” “—” means none. SIFT D: deleterious (); T: tolerated (). Polyphen2_HVAR D: probably damaging (≥0.909); P: possibly damaging (); B: benign (). Polyphen2_HDIV_pred D: probably damaging (≥0.957); P: possibly damaging (); B: benign (). MutationTaster_pred A: disease_causing_automatic; D: disease_causing; N: polymorphism; P: polymorphism_automatic. CADD13_PHRED D: ; InDel is not applicable. “EAS” means East Asian populations.