rs269855

Positions:

• chr15-45113789-G-A
• chr15-45113789-G-C
• chr15-45113789-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363711.2(DUOX2):​c.-15+184C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 152,202 control chromosomes in the GnomAD database, including 73,121 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.98 (73121 hom., cov: 30)
• Consequence: DUOX2 NM_001363711.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOX2	NM_001363711.2	c.-15+184C>T		intron_variant		ENST00000389039.11	NP_001350640.1
DUOX2	NM_014080.5	c.-15+184C>T		intron_variant			NP_054799.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUOX2	ENST00000389039.11	c.-15+184C>T		intron_variant		1	NM_001363711.2	ENSP00000373691	P4
DUOX2	ENST00000603300.1	c.-15+184C>T		intron_variant		1		ENSP00000475084	A1

Frequencies

GnomAD3 genomes AF: 0.980 AC: 149005 AN: 152086 Hom.: 73076 Cov.: 30

Gnomad AFR AF: 0.929

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.995

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.985

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.980 AC: 149105 AN: 152202 Hom.: 73121 Cov.: 30 AF XY: 0.981 AC XY: 72967 AN XY: 74400

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.995

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.985

Alfa AF: 0.997 Hom.: 59159

Bravo AF: 0.977

Asia WGS AF: 0.994 AC: 3457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.71
DANN	Benign	0.36

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

Other links and lift over

dbSNP: rs269855; hg19: chr15-45405987;