rs73406337

Variant names:

• chr15-45106116-G-A
• rs73406337
• NM_001363711.2:c.2148+9C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-45106116-G-A
• chr15-45106116-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.2148+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 1,613,674 control chromosomes in the GnomAD database, including 4,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (451 hom., cov: 32)
  • Exomes 𝑓: 0.071 (3949 hom.)
• Consequence: DUOX2 NM_001363711.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.77
• 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=-0.85).
• BP6: Variant 15-45106116-G-A is Benign according to our data. Variant chr15-45106116-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUOX2	NM_001363711.2	c.2148+9C>T		intron_variant	Intron 17 of 33	ENST00000389039.11	NP_001350640.1
DUOX2	NM_014080.5	c.2148+9C>T		intron_variant	Intron 17 of 33		NP_054799.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUOX2	ENST00000389039.11	c.2148+9C>T		intron_variant	Intron 17 of 33	1	NM_001363711.2	ENSP00000373691.7
DUOX2	ENST00000603300.1	c.2148+9C>T		intron_variant	Intron 17 of 33	1		ENSP00000475084.1
DUOX2	ENST00000558383.1	n.3879+9C>T		intron_variant	Intron 11 of 16	5

Frequencies

GnomAD3 genomes AF: 0.0743 AC: 11300 AN: 152154 Hom.: 450 Cov.: 32

Gnomad AFR AF: 0.0882

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.0519

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0725

Gnomad OTH AF: 0.0640

GnomAD2 exomes AF: 0.0673 AC: 16896 AN: 250964 AF XY: 0.0674

Gnomad AFR exome AF: 0.0873

Gnomad AMR exome AF: 0.0772

Gnomad ASJ exome AF: 0.0804

Gnomad EAS exome AF: 0.0250

Gnomad FIN exome AF: 0.0637

Gnomad NFE exome AF: 0.0709

Gnomad OTH exome AF: 0.0706

GnomAD4 exome AF: 0.0712 AC: 103986 AN: 1461402 Hom.: 3949 Cov.: 33 AF XY: 0.0708 AC XY: 51489 AN XY: 727054

African (AFR) AF: 0.0910 AC: 3044 AN: 33466

American (AMR) AF: 0.0794 AC: 3549 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.0780 AC: 2039 AN: 26130

East Asian (EAS) AF: 0.0386 AC: 1531 AN: 39698

South Asian (SAS) AF: 0.0551 AC: 4753 AN: 86230

European-Finnish (FIN) AF: 0.0629 AC: 3360 AN: 53396

Middle Eastern (MID) AF: 0.0717 AC: 411 AN: 5736

European-Non Finnish (NFE) AF: 0.0729 AC: 81043 AN: 1111676

Other (OTH) AF: 0.0705 AC: 4256 AN: 60374

GnomAD4 genome AF: 0.0744 AC: 11322 AN: 152272 Hom.: 451 Cov.: 32 AF XY: 0.0733 AC XY: 5461 AN XY: 74464

African (AFR) AF: 0.0882 AC: 3664 AN: 41550

American (AMR) AF: 0.0720 AC: 1102 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0833 AC: 289 AN: 3470

East Asian (EAS) AF: 0.0245 AC: 127 AN: 5176

South Asian (SAS) AF: 0.0520 AC: 251 AN: 4828

European-Finnish (FIN) AF: 0.0694 AC: 736 AN: 10606

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0726 AC: 4936 AN: 68018

Other (OTH) AF: 0.0671 AC: 142 AN: 2116

Alfa AF: 0.0666 Hom.: 202

Bravo AF: 0.0750

Asia WGS AF: 0.0530 AC: 185 AN: 3478

EpiCase AF: 0.0707

EpiControl AF: 0.0653

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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: Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.031
DANN	Benign	0.55
PhyloP100		-1.8
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: rs73406337; hg19: chr15-45398314; COSMIC: COSV66534169; COSMIC: COSV66534169;