rs56323146

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.4479C>G(p.Pro1493=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 1,613,836 control chromosomes in the GnomAD database, including 4,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1493P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.081 ( 570 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3635 hom. )

Consequence

DUOX2
NM_001363711.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.751

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=-0.69).

BP6

Variant 15-45094608-G-C is Benign according to our data. Variant chr15-45094608-G-C is described in ClinVar as [Benign]. Clinvar id is 260327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45094608-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.751 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUOX2	NM_001363711.2 linkuse as main transcript	c.4479C>G	p.Pro1493=	synonymous_variant	33/34	ENST00000389039.11
DUOX2	NM_014080.5 linkuse as main transcript	c.4479C>G	p.Pro1493=	synonymous_variant	33/34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUOX2	ENST00000389039.11 linkuse as main transcript	c.4479C>G	p.Pro1493=	synonymous_variant	33/34	1	NM_001363711.2	P4
DUOX2	ENST00000603300.1 linkuse as main transcript	c.4479C>G	p.Pro1493=	synonymous_variant	33/34	1		A1

Frequencies

GnomAD3 genomes

AF:

0.0808

AC:

12282

AN:

152054

Hom.:

569

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0662

Gnomad ASJ

AF:

0.0666

Gnomad EAS

AF:

0.0244

Gnomad SAS

AF:

0.0501

Gnomad FIN

AF:

0.0693

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0687

Gnomad OTH

AF:

0.0605

GnomAD3 exomes

AF:

0.0653

AC:

16386

AN:

250794

Hom.:

624

AF XY:

0.0644

AC XY:

8737

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.0726

Gnomad ASJ exome

AF:

0.0685

Gnomad EAS exome

AF:

0.0253

Gnomad SAS exome

AF:

0.0522

Gnomad FIN exome

AF:

0.0622

Gnomad NFE exome

AF:

0.0660

Gnomad OTH exome

AF:

0.0615

GnomAD4 exome

AF:

0.0681

AC:

99585

AN:

1461664

Hom.:

3635

Cov.:

AF XY:

0.0676

AC XY:

49134

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.0748

Gnomad4 ASJ exome

AF:

0.0649

Gnomad4 EAS exome

AF:

0.0387

Gnomad4 SAS exome

AF:

0.0527

Gnomad4 FIN exome

AF:

0.0623

Gnomad4 NFE exome

AF:

0.0690

Gnomad4 OTH exome

AF:

0.0667

GnomAD4 genome

AF:

0.0808

AC:

12301

AN:

152172

Hom.:

570

Cov.:

AF XY:

0.0796

AC XY:

5922

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.0664

Gnomad4 ASJ

AF:

0.0666

Gnomad4 EAS

AF:

0.0244

Gnomad4 SAS

AF:

0.0500

Gnomad4 FIN

AF:

0.0693

Gnomad4 NFE

AF:

0.0687

Gnomad4 OTH

AF:

0.0632

Alfa

AF:

0.0575

Hom.:

118

Bravo

AF:

0.0815

Asia WGS

AF:

0.0530

AC:

186

AN:

3478

EpiCase

AF:

0.0634

EpiControl

AF:

0.0573

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Thyroid dyshormonogenesis 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.7

DANN

Benign

0.61

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