15-45093559-G-A

Variant names:

• chr15-45093559-G-A
• rs11070441
• NM_001363711.2:c.*591C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001363711.2(DUOX2):​c.*591C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 155,266 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (122 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (0 hom.)
• Consequence: DUOX2 NM_001363711.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.712
• 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• familial thyroid dyshormonogenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-45093559-G-A is Benign according to our data. Variant chr15-45093559-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 885813.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363711.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUOX2	NM_001363711.2	MANE Select	c.*591C>T		3_prime_UTR	Exon 34 of 34	NP_001350640.1	X6RAN8
	DUOX2	NM_014080.5		c.*591C>T		3_prime_UTR	Exon 34 of 34	NP_054799.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUOX2	ENST00000389039.11	TSL:1 MANE Select	c.*591C>T		3_prime_UTR	Exon 34 of 34	ENSP00000373691.7	X6RAN8
	DUOX2	ENST00000603300.1	TSL:1	c.*591C>T		3_prime_UTR	Exon 34 of 34	ENSP00000475084.1	Q9NRD8

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 3306 AN: 152078 Hom.: 123 Cov.: 32

Gnomad AFR AF: 0.0743

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00904

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00769

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00261 AC: 8 AN: 3070 Hom.: 0 Cov.: 0 AF XY: 0.00243 AC XY: 4 AN XY: 1646

African (AFR) AF: 0.0676 AC: 5 AN: 74

American (AMR) AF: 0.00464 AC: 3 AN: 646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14

East Asian (EAS) AF: 0.00 AC: 0 AN: 128

South Asian (SAS) AF: 0.00 AC: 0 AN: 160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1902

Other (OTH) AF: 0.00 AC: 0 AN: 110

GnomAD4 genome AF: 0.0218 AC: 3313 AN: 152196 Hom.: 122 Cov.: 32 AF XY: 0.0208 AC XY: 1545 AN XY: 74420

African (AFR) AF: 0.0743 AC: 3082 AN: 41502

American (AMR) AF: 0.00903 AC: 138 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00790 AC: 41 AN: 5188

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68004

Other (OTH) AF: 0.0137 AC: 29 AN: 2114

Alfa AF: 0.00618 Hom.: 29

Bravo AF: 0.0247

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Thyroid dyshormonogenesis 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.41
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs11070441; hg19: chr15-45385757;