rs73406337

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000389039.11(DUOX2):c.2148+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 1,613,674 control chromosomes in the GnomAD database, including 4,400 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 ( 451 hom., cov: 32)

Exomes 𝑓: 0.071 ( 3949 hom. )

Consequence

DUOX2
ENST00000389039.11 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.77

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 15-45106116-G-A is Benign according to our data. Variant chr15-45106116-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45106116-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOX2	NM_001363711.2 linkuse as main transcript	c.2148+9C>T		intron_variant		ENST00000389039.11	NP_001350640.1
DUOX2	NM_014080.5 linkuse as main transcript	c.2148+9C>T		intron_variant			NP_054799.4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
DUOX2	ENST00000389039.11 linkuse as main transcript	c.2148+9C>T	intron_variant	1	NM_001363711.2	ENSP00000373691	P4
DUOX2	ENST00000603300.1 linkuse as main transcript	c.2148+9C>T	intron_variant	1		ENSP00000475084	A1
DUOX2	ENST00000558383.1 linkuse as main transcript	n.3879+9C>T	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0743

AC:

11300

AN:

152154

Hom.:

450

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0882

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0718

Gnomad ASJ

AF:

0.0833

Gnomad EAS

AF:

0.0245

Gnomad SAS

AF:

0.0519

Gnomad FIN

AF:

0.0694

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0725

Gnomad OTH

AF:

0.0640

GnomAD3 exomes

AF:

0.0673

AC:

16896

AN:

250964

Hom.:

670

AF XY:

0.0674

AC XY:

9140

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.0873

Gnomad AMR exome

AF:

0.0772

Gnomad ASJ exome

AF:

0.0804

Gnomad EAS exome

AF:

0.0250

Gnomad SAS exome

AF:

0.0554

Gnomad FIN exome

AF:

0.0637

Gnomad NFE exome

AF:

0.0709

Gnomad OTH exome

AF:

0.0706

GnomAD4 exome

AF:

0.0712

AC:

103986

AN:

1461402

Hom.:

3949

Cov.:

AF XY:

0.0708

AC XY:

51489

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.0910

Gnomad4 AMR exome

AF:

0.0794

Gnomad4 ASJ exome

AF:

0.0780

Gnomad4 EAS exome

AF:

0.0386

Gnomad4 SAS exome

AF:

0.0551

Gnomad4 FIN exome

AF:

0.0629

Gnomad4 NFE exome

AF:

0.0729

Gnomad4 OTH exome

AF:

0.0705

GnomAD4 genome

AF:

0.0744

AC:

11322

AN:

152272

Hom.:

451

Cov.:

AF XY:

0.0733

AC XY:

5461

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0882

Gnomad4 AMR

AF:

0.0720

Gnomad4 ASJ

AF:

0.0833

Gnomad4 EAS

AF:

0.0245

Gnomad4 SAS

AF:

0.0520

Gnomad4 FIN

AF:

0.0694

Gnomad4 NFE

AF:

0.0726

Gnomad4 OTH

AF:

0.0671

Alfa

AF:

0.0665

Hom.:

200

Bravo

AF:

0.0750

Asia WGS

AF:

0.0530

AC:

185

AN:

3478

EpiCase

AF:

0.0707

EpiControl

AF:

0.0653

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 09, 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

-0.85

CADD

Benign

0.031

DANN

Benign

0.55

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