rs73406334

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001363711.2(DUOX2):c.2286G>A(p.Gln762Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0716 in 1,614,176 control chromosomes in the GnomAD database, including 4,412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.074 ( 453 hom., cov: 32)

Exomes 𝑓: 0.071 ( 3959 hom. )

Consequence

DUOX2
NM_001363711.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.78

Publications

7 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 15-45105691-C-T is Benign according to our data. Variant chr15-45105691-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.78 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUOX2	NM_001363711.2 link	c.2286G>A	p.Gln762Gln	synonymous_variant	Exon 18 of 34	ENST00000389039.11	NP_001350640.1
DUOX2	NM_014080.5 link	c.2286G>A	p.Gln762Gln	synonymous_variant	Exon 18 of 34		NP_054799.4	Q9NRD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DUOX2	ENST00000389039.11 link	c.2286G>A	p.Gln762Gln	synonymous_variant	Exon 18 of 34	1	NM_001363711.2	ENSP00000373691.7	X6RAN8
DUOX2	ENST00000603300.1 link	c.2286G>A	p.Gln762Gln	synonymous_variant	Exon 18 of 34	1		ENSP00000475084.1	Q9NRD8
DUOX2	ENST00000558383.1 link	n.4017G>A		non_coding_transcript_exon_variant	Exon 12 of 17	5

Frequencies

GnomAD3 genomes

AF:

0.0743

AC:

11307

AN:

152182

Hom.:

452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0883

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0718

Gnomad ASJ

AF:

0.0830

Gnomad EAS

AF:

0.0248

Gnomad SAS

AF:

0.0520

Gnomad FIN

AF:

0.0695

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0725

Gnomad OTH

AF:

0.0641

GnomAD2 exomes

AF:

0.0675

AC:

16969

AN:

251466

AF XY:

0.0676

show subpopulations

Gnomad AFR exome

AF:

0.0872

Gnomad AMR exome

AF:

0.0775

Gnomad ASJ exome

AF:

0.0805

Gnomad EAS exome

AF:

0.0251

Gnomad FIN exome

AF:

0.0638

Gnomad NFE exome

AF:

0.0710

Gnomad OTH exome

AF:

0.0708

GnomAD4 exome

AF:

0.0713

AC:

104171

AN:

1461876

Hom.:

3959

Cov.:

AF XY:

0.0709

AC XY:

51560

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.0910

AC:

3047

AN:

33480

American (AMR)

AF:

0.0796

AC:

3560

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0781

AC:

2040

AN:

26136

East Asian (EAS)

AF:

0.0386

AC:

1531

AN:

39700

South Asian (SAS)

AF:

0.0554

AC:

4779

AN:

86258

European-Finnish (FIN)

AF:

0.0630

AC:

3364

AN:

53414

Middle Eastern (MID)

AF:

0.0725

AC:

418

AN:

5768

European-Non Finnish (NFE)

AF:

0.0730

AC:

81169

AN:

1112000

Other (OTH)

AF:

0.0706

AC:

4263

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

6134

12268

18403

24537

30671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3052

6104

9156

12208

15260

<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:

0.0744

AC:

11329

AN:

152300

Hom.:

453

Cov.:

AF XY:

0.0733

AC XY:

5456

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0883

AC:

3670

AN:

41562

American (AMR)

AF:

0.0720

AC:

1102

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0830

AC:

288

AN:

3470

East Asian (EAS)

AF:

0.0249

AC:

129

AN:

5186

South Asian (SAS)

AF:

0.0520

AC:

251

AN:

4824

European-Finnish (FIN)

AF:

0.0695

AC:

738

AN:

10612

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0725

AC:

4934

AN:

68024

Other (OTH)

AF:

0.0672

AC:

142

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

569

1138

1706

2275

2844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0741

Hom.:

366

Bravo

AF:

0.0750

Asia WGS

AF:

0.0530

AC:

184

AN:

3478

EpiCase

AF:

0.0705

EpiControl

AF:

0.0654

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Thyroid dyshormonogenesis 6

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

8.7

(source)

DANN

Benign

0.75

PhyloP100

1.8

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over