rs73406330

Variant names:

• chr15-45105633-G-A
• rs73406330
• NM_001363711.2:c.2334+10C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-45105633-G-A
• chr15-45105633-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001363711.2(DUOX2):​c.2334+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0885 in 1,613,860 control chromosomes in the GnomAD database, including 9,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2930 hom., cov: 32)
  • Exomes 𝑓: 0.082 (6613 hom.)
• Consequence: DUOX2 NM_001363711.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.53
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 15-45105633-G-A is Benign according to our data. Variant chr15-45105633-G-A is described in ClinVar as Benign. ClinVar VariationId is 260321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUOX2	NM_001363711.2	c.2334+10C>T		intron_variant	Intron 18 of 33	ENST00000389039.11	NP_001350640.1
DUOX2	NM_014080.5	c.2334+10C>T		intron_variant	Intron 18 of 33		NP_054799.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUOX2	ENST00000389039.11	c.2334+10C>T		intron_variant	Intron 18 of 33	1	NM_001363711.2	ENSP00000373691.7
DUOX2	ENST00000603300.1	c.2334+10C>T		intron_variant	Intron 18 of 33	1		ENSP00000475084.1
DUOX2	ENST00000558383.1	n.4065+10C>T		intron_variant	Intron 12 of 16	5

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22991 AN: 152010 Hom.: 2915 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0850

Gnomad EAS AF: 0.0513

Gnomad SAS AF: 0.0557

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.127

GnomAD2 exomes AF: 0.0946 AC: 23745 AN: 250904 AF XY: 0.0886

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.0813

Gnomad EAS exome AF: 0.0503

Gnomad FIN exome AF: 0.0686

Gnomad NFE exome AF: 0.0736

Gnomad OTH exome AF: 0.0869

GnomAD4 exome AF: 0.0820 AC: 119845 AN: 1461732 Hom.: 6613 Cov.: 33 AF XY: 0.0805 AC XY: 58507 AN XY: 727182

African (AFR) AF: 0.359 AC: 12025 AN: 33476

American (AMR) AF: 0.121 AC: 5405 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0791 AC: 2067 AN: 26134

East Asian (EAS) AF: 0.0554 AC: 2200 AN: 39700

South Asian (SAS) AF: 0.0595 AC: 5136 AN: 86250

European-Finnish (FIN) AF: 0.0680 AC: 3633 AN: 53388

Middle Eastern (MID) AF: 0.0920 AC: 530 AN: 5764

European-Non Finnish (NFE) AF: 0.0748 AC: 83173 AN: 1111912

Other (OTH) AF: 0.0940 AC: 5676 AN: 60388

GnomAD4 genome AF: 0.152 AC: 23056 AN: 152128 Hom.: 2930 Cov.: 32 AF XY: 0.148 AC XY: 11038 AN XY: 74406

African (AFR) AF: 0.344 AC: 14269 AN: 41434

American (AMR) AF: 0.111 AC: 1704 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0850 AC: 295 AN: 3472

East Asian (EAS) AF: 0.0512 AC: 265 AN: 5176

South Asian (SAS) AF: 0.0562 AC: 271 AN: 4824

European-Finnish (FIN) AF: 0.0759 AC: 805 AN: 10602

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0749 AC: 5091 AN: 68008

Other (OTH) AF: 0.131 AC: 277 AN: 2112

Alfa AF: 0.0984 Hom.: 464

Bravo AF: 0.163

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Thyroid dyshormonogenesis 6 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.78
CADD	Benign	0.63
DANN	Benign	0.74
PhyloP100		-1.5
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: rs73406330; hg19: chr15-45397831;