rs61730032

Positions:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 260325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45095942-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
DUOX2	NM_001363711.2 link	c.3966C>T	p.Ser1322Ser	synonymous_variant	30/34	ENST00000389039.11	NP_001350640.1
DUOX2	NM_014080.5 link	c.3966C>T	p.Ser1322Ser	synonymous_variant	30/34		NP_054799.4	Q9NRD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUOX2	ENST00000389039.11 link	c.3966C>T	p.Ser1322Ser	synonymous_variant	30/34	1	NM_001363711.2	ENSP00000373691.7		X6RAN8
DUOX2	ENST00000603300.1 link	c.3966C>T	p.Ser1322Ser	synonymous_variant	30/34	1		ENSP00000475084.1		Q9NRD8

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

GnomAD3 exomes

AF:

0.0149

AC:

3737

AN:

251476

Hom.:

AF XY:

0.0142

AC XY:

1926

AN XY:

135912

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 SAS exome

AF:

0.0119

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

Gnomad4 AFR exome

AF:

0.0598

Gnomad4 AMR exome

AF:

0.00604

Gnomad4 ASJ exome

AF:

0.00532

Gnomad4 EAS exome

AF:

0.0385

Gnomad4 SAS exome

AF:

0.0116

Gnomad4 FIN exome

AF:

0.00569

Gnomad4 NFE exome

AF:

0.0149

Gnomad4 OTH exome

AF:

0.0174

GnomAD4 genome

AF:

0.0251

AC:

3820

AN:

152076

Hom.:

Cov.:

AF XY:

0.0241

AC XY:

1792

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0579

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.0234

Gnomad4 SAS

AF:

0.0119

Gnomad4 FIN

AF:

0.00461

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.0161

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Thyroid dyshormonogenesis 6

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

DANN

Benign

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over