rs269855

Variant names:

• chr15-45113789-G-A
• rs269855
• NM_001363711.2:c.-15+184C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• thyroid dyshormonogenesis 6

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• familial thyroid dyshormonogenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DUOX2	NM_001363711.2	c.-15+184C>T		intron_variant	Intron 1 of 33	ENST00000389039.11	NP_001350640.1
DUOX2	NM_014080.5	c.-15+184C>T		intron_variant	Intron 1 of 33		NP_054799.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUOX2	ENST00000389039.11	c.-15+184C>T		intron_variant	Intron 1 of 33	1	NM_001363711.2	ENSP00000373691.7
DUOX2	ENST00000603300.1	c.-15+184C>T		intron_variant	Intron 1 of 33	1		ENSP00000475084.1

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

African (AFR) AF: 0.928 AC: 38543 AN: 41512

American (AMR) AF: 0.995 AC: 15213 AN: 15296

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5142 AN: 5142

South Asian (SAS) AF: 1.00 AC: 4824 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10610 AN: 10610

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68014 AN: 68026

Other (OTH) AF: 0.985 AC: 2082 AN: 2114

Alfa AF: 0.994 Hom.: 81356

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
PhyloP100		-0.60
PromoterAI		-0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs269855; hg19: chr15-45405987;