NM_001363711.2:c.3966C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001363711.2(DUOX2):c.3966C>T(p.Ser1322Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,613,966 control chromosomes in the GnomAD database, including 359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 84 hom., cov: 31)

Exomes 𝑓: 0.016 ( 275 hom. )

Consequence

DUOX2
NM_001363711.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.24

Publications

2 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 15-45095942-G-A is Benign according to our data. Variant chr15-45095942-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUOX2	NM_001363711.2 link	c.3966C>T	p.Ser1322Ser	synonymous_variant	Exon 30 of 34	ENST00000389039.11	NP_001350640.1
DUOX2	NM_014080.5 link	c.3966C>T	p.Ser1322Ser	synonymous_variant	Exon 30 of 34		NP_054799.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUOX2	ENST00000389039.11 link	c.3966C>T	p.Ser1322Ser	synonymous_variant	Exon 30 of 34	1	NM_001363711.2	ENSP00000373691.7
DUOX2	ENST00000603300.1 link	c.3966C>T	p.Ser1322Ser	synonymous_variant	Exon 30 of 34	1		ENSP00000475084.1

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3805

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.0234

Gnomad SAS

AF:

0.0119

Gnomad FIN

AF:

0.00461

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.0149

AC:

3737

AN:

251476

AF XY:

0.0142

show subpopulations

Gnomad AFR exome

AF:

0.0579

Gnomad AMR exome

AF:

0.00526

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.0252

Gnomad FIN exome

AF:

0.00504

Gnomad NFE exome

AF:

0.0136

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.0156

AC:

22858

AN:

1461890

Hom.:

275

Cov.:

AF XY:

0.0153

AC XY:

11101

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.0598

AC:

2002

AN:

33478

American (AMR)

AF:

0.00604

AC:

270

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00532

AC:

139

AN:

26136

East Asian (EAS)

AF:

0.0385

AC:

1527

AN:

39700

South Asian (SAS)

AF:

0.0116

AC:

1002

AN:

86258

European-Finnish (FIN)

AF:

0.00569

AC:

304

AN:

53420

Middle Eastern (MID)

AF:

0.00520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0149

AC:

16536

AN:

1112010

Other (OTH)

AF:

0.0174

AC:

1048

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1488

2976

4463

5951

7439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.0251

AC:

3820

AN:

152076

Hom.:

Cov.:

AF XY:

0.0241

AC XY:

1792

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0579

AC:

2402

AN:

41458

American (AMR)

AF:

0.0111

AC:

169

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3470

East Asian (EAS)

AF:

0.0234

AC:

121

AN:

5160

South Asian (SAS)

AF:

0.0119

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00461

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0141

AC:

957

AN:

67976

Other (OTH)

AF:

0.0161

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

178

357

535

714

892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0199

Hom.:

Bravo

AF:

0.0267

Asia WGS

AF:

0.0360

AC:

127

AN:

3478

EpiCase

AF:

0.0130

EpiControl

AF:

0.0101

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 14, 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

- -

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

-0.84

CADD

Benign

0.094

(source)

DANN

Benign

0.60

PhyloP100

-2.2

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over