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: 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 -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.

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.2148+9C>T		intron	N/A	NP_001350640.1	X6RAN8
	DUOX2	NM_014080.5		c.2148+9C>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.2148+9C>T		intron	N/A	ENSP00000373691.7	X6RAN8
	DUOX2	ENST00000603300.1	TSL:1	c.2148+9C>T		intron	N/A	ENSP00000475084.1	Q9NRD8
	DUOX2	ENST00000558383.1	TSL:5	n.3879+9C>T		intron	N/A

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	Thyroid dyshormonogenesis 6 (1)

Computational scores

Source: dbNSFP v4.9

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;