NM_001363711.2:c.2102G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001363711.2(DUOX2):c.2102G>A(p.Arg701Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0548 in 1,614,058 control chromosomes in the GnomAD database, including 2,712 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R701L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.049 ( 237 hom., cov: 32)

Exomes 𝑓: 0.055 ( 2475 hom. )

Consequence

DUOX2
NM_001363711.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.38

Publications

14 publications found

Variant links:

Genes affected

DUOX2 (HGNC:13273): (dual oxidase 2) The protein encoded by this gene is a glycoprotein and a member of the NADPH oxidase family. The synthesis of thyroid hormone is catalyzed by a protein complex located at the apical membrane of thyroid follicular cells. This complex contains an iodide transporter, thyroperoxidase, and a peroxide generating system that includes this encoded protein and DUOX1. This protein is known as dual oxidase because it has both a peroxidase homology domain and a gp91phox domain. [provided by RefSeq, Jul 2008]

DUOX2 Gene-Disease associations (from GenCC):

thyroid dyshormonogenesis 6
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
familial thyroid dyshormonogenesis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DUOX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001822114).

BP6

Variant 15-45106171-C-T is Benign according to our data. Variant chr15-45106171-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0571 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363711.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUOX2	NM_001363711.2	MANE Select	c.2102G>A	p.Arg701Gln	missense	Exon 17 of 34	NP_001350640.1
	DUOX2	NM_014080.5		c.2102G>A	p.Arg701Gln	missense	Exon 17 of 34	NP_054799.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DUOX2	ENST00000389039.11	TSL:1 MANE Select	c.2102G>A	p.Arg701Gln	missense	Exon 17 of 34	ENSP00000373691.7
DUOX2	ENST00000603300.1	TSL:1	c.2102G>A	p.Arg701Gln	missense	Exon 17 of 34	ENSP00000475084.1
DUOX2	ENST00000558383.1	TSL:5	n.3833G>A		non_coding_transcript_exon	Exon 11 of 17

Frequencies

GnomAD3 genomes

AF:

0.0492

AC:

7483

AN:

152100

Hom.:

236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0309

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0601

Gnomad ASJ

AF:

0.0740

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0401

Gnomad FIN

AF:

0.0647

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0582

Gnomad OTH

AF:

0.0508

GnomAD2 exomes

AF:

0.0525

AC:

13188

AN:

251334

AF XY:

0.0532

show subpopulations

Gnomad AFR exome

AF:

0.0295

Gnomad AMR exome

AF:

0.0720

Gnomad ASJ exome

AF:

0.0752

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.0588

Gnomad NFE exome

AF:

0.0574

Gnomad OTH exome

AF:

0.0574

GnomAD4 exome

AF:

0.0554

AC:

80962

AN:

1461840

Hom.:

2475

Cov.:

AF XY:

0.0554

AC XY:

40255

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.0313

AC:

1047

AN:

33480

American (AMR)

AF:

0.0733

AC:

3279

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0727

AC:

1899

AN:

26136

East Asian (EAS)

AF:

0.000277

AC:

AN:

39700

South Asian (SAS)

AF:

0.0431

AC:

3719

AN:

86254

European-Finnish (FIN)

AF:

0.0573

AC:

3058

AN:

53412

Middle Eastern (MID)

AF:

0.0671

AC:

387

AN:

5768

European-Non Finnish (NFE)

AF:

0.0579

AC:

64365

AN:

1111974

Other (OTH)

AF:

0.0529

AC:

3197

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

4795

9589

14384

19178

23973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2404

4808

7212

9616

12020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0492

AC:

7490

AN:

152218

Hom.:

237

Cov.:

AF XY:

0.0491

AC XY:

3655

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0309

AC:

1282

AN:

41544

American (AMR)

AF:

0.0604

AC:

923

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0740

AC:

257

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5178

South Asian (SAS)

AF:

0.0401

AC:

193

AN:

4812

European-Finnish (FIN)

AF:

0.0647

AC:

686

AN:

10600

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0583

AC:

3962

AN:

68004

Other (OTH)

AF:

0.0502

AC:

106

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

363

725

1088

1450

1813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0537

Hom.:

481

Bravo

AF:

0.0484

TwinsUK

AF:

0.0534

AC:

198

ALSPAC

AF:

0.0566

AC:

218

ESP6500AA

AF:

0.0318

AC:

140

ESP6500EA

AF:

0.0587

AC:

505

ExAC

AF:

0.0504

AC:

6120

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0570

EpiControl

AF:

0.0550

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Thyroid dyshormonogenesis 6 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

-1.4

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.96

REVEL

Benign

0.058

Sift

Benign

0.21

Sift4G

Benign

0.34

Polyphen

0.17

Vest4

0.042

MPC

0.095

ClinPred

0.0050

GERP RS

-2.0

Varity_R

0.043

gMVP

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over