15-45106171-C-T

Position:

chr15-45106171-C-T

Variant summary

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

The NM_001363711.2(DUOX2):c.2102G>A(p.Arg701Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0548 in 1,614,058 control chromosomes in the GnomAD database, including 2,712 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 237 hom., cov: 32)

Exomes 𝑓: 0.055 ( 2475 hom. )

Consequence

DUOX2
NM_001363711.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.38

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:

DUOX2 (HGNC:):

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 (MetaRNN=0.001822114).

BP6

Variant 15-45106171-C-T is Benign according to our data. Variant chr15-45106171-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45106171-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0571 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.2102G>A	p.Arg701Gln	missense_variant	17/34	ENST00000389039.11	NP_001350640.1
DUOX2	NM_014080.5 linkuse as main transcript	c.2102G>A	p.Arg701Gln	missense_variant	17/34		NP_054799.4	Q9NRD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DUOX2	ENST00000389039.11 linkuse as main transcript	c.2102G>A	p.Arg701Gln	missense_variant	17/34	1	NM_001363711.2	ENSP00000373691.7	X6RAN8
DUOX2	ENST00000603300.1 linkuse as main transcript	c.2102G>A	p.Arg701Gln	missense_variant	17/34	1		ENSP00000475084.1	Q9NRD8
DUOX2	ENST00000558383.1 linkuse as main transcript	n.3833G>A		non_coding_transcript_exon_variant	11/17	5

Frequencies

GnomAD3 genomes

AF:

0.0492

AC:

7483

AN:

152100

Hom.:

236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0309

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0601

Gnomad ASJ

AF:

0.0740

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0401

Gnomad FIN

AF:

0.0647

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0582

Gnomad OTH

AF:

0.0508

GnomAD3 exomes

AF:

0.0525

AC:

13188

AN:

251334

Hom.:

442

AF XY:

0.0532

AC XY:

7223

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.0295

Gnomad AMR exome

AF:

0.0720

Gnomad ASJ exome

AF:

0.0752

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0429

Gnomad FIN exome

AF:

0.0588

Gnomad NFE exome

AF:

0.0574

Gnomad OTH exome

AF:

0.0574

GnomAD4 exome

AF:

0.0554

AC:

80962

AN:

1461840

Hom.:

2475

Cov.:

AF XY:

0.0554

AC XY:

40255

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0313

Gnomad4 AMR exome

AF:

0.0733

Gnomad4 ASJ exome

AF:

0.0727

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0431

Gnomad4 FIN exome

AF:

0.0573

Gnomad4 NFE exome

AF:

0.0579

Gnomad4 OTH exome

AF:

0.0529

GnomAD4 genome

AF:

0.0492

AC:

7490

AN:

152218

Hom.:

237

Cov.:

AF XY:

0.0491

AC XY:

3655

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0309

Gnomad4 AMR

AF:

0.0604

Gnomad4 ASJ

AF:

0.0740

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0401

Gnomad4 FIN

AF:

0.0647

Gnomad4 NFE

AF:

0.0583

Gnomad4 OTH

AF:

0.0502

Alfa

AF:

0.0542

Hom.:

357

Bravo

AF:

0.0484

TwinsUK

AF:

0.0534

AC:

198

ALSPAC

AF:

0.0566

AC:

218

ESP6500AA

AF:

0.0318

AC:

140

ESP6500EA

AF:

0.0587

AC:

505

ExAC

AF:

0.0504

AC:

6120

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0570

EpiControl

AF:

0.0550

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	GeneDx	Jul 09, 2018	This variant is associated with the following publications: (PMID: 28666341) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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 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 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

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

.;M

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.96

N;.

REVEL

Benign

0.058

Sift

Benign

0.21

T;.

Sift4G

Benign

0.34

T;T

Polyphen

0.17

.;B

Vest4

0.042

MPC

0.095

ClinPred

0.0050

GERP RS

-2.0

Varity_R

0.043

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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