NM_001363711.2:c.2334+10C>T

Variant names:

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

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.2334+10C>T		intron	N/A	NP_001350640.1
	DUOX2	NM_014080.5		c.2334+10C>T		intron	N/A	NP_054799.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUOX2	ENST00000389039.11	TSL:1 MANE Select	c.2334+10C>T		intron	N/A	ENSP00000373691.7
	DUOX2	ENST00000603300.1	TSL:1	c.2334+10C>T		intron	N/A	ENSP00000475084.1
	DUOX2	ENST00000558383.1	TSL:5	n.4065+10C>T		intron	N/A

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Thyroid dyshormonogenesis 6 (1)

Computational scores

Source: dbNSFP v4.9

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;