Variant 15-45093718-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001363711.2(DUOX2):c.*432G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 193,802 control chromosomes in the GnomAD database, including 7,738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 7283 hom., cov: 32)

Exomes 𝑓: 0.091 ( 455 hom. )

Consequence

DUOX2
NM_001363711.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.05

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=-0.9).

BP6

Variant 15-45093718-C-T is Benign according to our data. Variant chr15-45093718-C-T is described in ClinVar as [Benign]. Clinvar id is 316130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 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.*432G>A		3_prime_UTR_variant	34/34	ENST00000389039.11	NP_001350640.1
DUOX2	NM_014080.5 linkuse as main transcript	c.*432G>A		3_prime_UTR_variant	34/34		NP_054799.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUOX2	ENST00000389039.11 linkuse as main transcript	c.*432G>A		3_prime_UTR_variant	34/34	1	NM_001363711.2	ENSP00000373691	P4
DUOX2	ENST00000603300.1 linkuse as main transcript	c.*432G>A		3_prime_UTR_variant	34/34	1		ENSP00000475084	A1

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32209

AN:

151952

Hom.:

7256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.0686

Gnomad EAS

AF:

0.0495

Gnomad SAS

AF:

0.0534

Gnomad FIN

AF:

0.0756

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0710

Gnomad OTH

AF:

0.155

GnomAD4 exome

AF:

0.0909

AC:

3794

AN:

41732

Hom.:

455

Cov.:

AF XY:

0.0859

AC XY:

1888

AN XY:

21988

show subpopulations

Gnomad4 AFR exome

AF:

0.573

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.0535

Gnomad4 EAS exome

AF:

0.0452

Gnomad4 SAS exome

AF:

0.0501

Gnomad4 FIN exome

AF:

0.0489

Gnomad4 NFE exome

AF:

0.0618

Gnomad4 OTH exome

AF:

0.0910

GnomAD4 genome

AF:

0.212

AC:

32293

AN:

152070

Hom.:

7283

Cov.:

AF XY:

0.206

AC XY:

15344

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.570

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.0686

Gnomad4 EAS

AF:

0.0494

Gnomad4 SAS

AF:

0.0536

Gnomad4 FIN

AF:

0.0756

Gnomad4 NFE

AF:

0.0710

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.0901

Hom.:

1516

Bravo

AF:

0.232

Asia WGS

AF:

0.124

AC:

431

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.90

CADD

Benign

0.15

DANN

Benign

0.51

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