15-45108160-C-G

Position:

chr15-45108160-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001363711.2(DUOX2):c.1461G>C(p.Gly487Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 1,614,096 control chromosomes in the GnomAD database, including 741,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 60167 hom., cov: 32)

Exomes 𝑓: 0.96 ( 680879 hom. )

Consequence

DUOX2
NM_001363711.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.224

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 15-45108160-C-G is Benign according to our data. Variant chr15-45108160-C-G is described in ClinVar as [Benign]. Clinvar id is 260315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45108160-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.224 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.966 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.1461G>C	p.Gly487Gly	synonymous_variant	13/34	ENST00000389039.11	NP_001350640.1
DUOX2	NM_014080.5 linkuse as main transcript	c.1461G>C	p.Gly487Gly	synonymous_variant	13/34		NP_054799.4	Q9NRD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DUOX2	ENST00000389039.11 linkuse as main transcript	c.1461G>C	p.Gly487Gly	synonymous_variant	13/34	1	NM_001363711.2	ENSP00000373691.7	X6RAN8
DUOX2	ENST00000603300.1 linkuse as main transcript	c.1461G>C	p.Gly487Gly	synonymous_variant	13/34	1		ENSP00000475084.1	Q9NRD8
DUOX2	ENST00000558383.1 linkuse as main transcript	n.3192G>C		non_coding_transcript_exon_variant	7/17	5

Frequencies

GnomAD3 genomes

AF:

0.875

AC:

133070

AN:

152104

Hom.:

60155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.620

Gnomad AMI

AF:

0.992

Gnomad AMR

AF:

0.944

Gnomad ASJ

AF:

0.997

Gnomad EAS

AF:

0.977

Gnomad SAS

AF:

0.987

Gnomad FIN

AF:

0.986

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.972

Gnomad OTH

AF:

0.904

GnomAD3 exomes

AF:

0.949

AC:

238478

AN:

251416

Hom.:

114187

AF XY:

0.957

AC XY:

130036

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.610

Gnomad AMR exome

AF:

0.945

Gnomad ASJ exome

AF:

0.997

Gnomad EAS exome

AF:

0.979

Gnomad SAS exome

AF:

0.986

Gnomad FIN exome

AF:

0.985

Gnomad NFE exome

AF:

0.971

Gnomad OTH exome

AF:

0.966

GnomAD4 exome

AF:

0.964

AC:

1408581

AN:

1461874

Hom.:

680879

Cov.:

AF XY:

0.966

AC XY:

702298

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.614

Gnomad4 AMR exome

AF:

0.944

Gnomad4 ASJ exome

AF:

0.996

Gnomad4 EAS exome

AF:

0.985

Gnomad4 SAS exome

AF:

0.986

Gnomad4 FIN exome

AF:

0.984

Gnomad4 NFE exome

AF:

0.971

Gnomad4 OTH exome

AF:

0.955

GnomAD4 genome

AF:

0.875

AC:

133119

AN:

152222

Hom.:

60167

Cov.:

AF XY:

0.881

AC XY:

65592

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.619

Gnomad4 AMR

AF:

0.944

Gnomad4 ASJ

AF:

0.997

Gnomad4 EAS

AF:

0.977

Gnomad4 SAS

AF:

0.986

Gnomad4 FIN

AF:

0.986

Gnomad4 NFE

AF:

0.972

Gnomad4 OTH

AF:

0.904

Alfa

AF:

0.942

Hom.:

7566

Bravo

AF:

0.859

Asia WGS

AF:

0.925

AC:

3216

AN:

3478

EpiCase

AF:

0.974

EpiControl

AF:

0.973

ClinVar

Significance: Benign

Submissions summary: Benign:8

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 05, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Thyroid dyshormonogenesis 6

Benign:3

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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. -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

4.9

DANN

Benign

0.73

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