chr15-45093718-C-T

Variant names:

• chr15-45093718-C-T
• rs10851420
• NM_001363711.2:c.*432G>A

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.*432G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 193,802 control chromosomes in the GnomAD database, including 7,738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (7283 hom., cov: 32)
  • Exomes 𝑓: 0.091 (455 hom.)
• Consequence: DUOX2 NM_001363711.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.05
• Publications: 9 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=-0.9).
• BP6: Variant 15-45093718-C-T is Benign according to our data. Variant chr15-45093718-C-T is described in ClinVar as Benign. ClinVar VariationId is 316130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 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.*432G>A		3_prime_UTR	Exon 34 of 34	NP_001350640.1	X6RAN8
	DUOX2	NM_014080.5		c.*432G>A		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.*432G>A		3_prime_UTR	Exon 34 of 34	ENSP00000373691.7	X6RAN8
	DUOX2	ENST00000603300.1	TSL:1	c.*432G>A		3_prime_UTR	Exon 34 of 34	ENSP00000475084.1	Q9NRD8

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32209 AN: 151952 Hom.: 7256 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.0495

Gnomad SAS AF: 0.0534

Gnomad FIN AF: 0.0756

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.0909 AC: 3794 AN: 41732 Hom.: 455 Cov.: 0 AF XY: 0.0859 AC XY: 1888 AN XY: 21988

African (AFR) AF: 0.573 AC: 1216 AN: 2122

American (AMR) AF: 0.118 AC: 403 AN: 3402

Ashkenazi Jewish (ASJ) AF: 0.0535 AC: 58 AN: 1084

East Asian (EAS) AF: 0.0452 AC: 125 AN: 2766

South Asian (SAS) AF: 0.0501 AC: 233 AN: 4648

European-Finnish (FIN) AF: 0.0489 AC: 65 AN: 1328

Middle Eastern (MID) AF: 0.0800 AC: 12 AN: 150

European-Non Finnish (NFE) AF: 0.0618 AC: 1495 AN: 24176

Other (OTH) AF: 0.0910 AC: 187 AN: 2056

GnomAD4 genome AF: 0.212 AC: 32293 AN: 152070 Hom.: 7283 Cov.: 32 AF XY: 0.206 AC XY: 15344 AN XY: 74348

African (AFR) AF: 0.570 AC: 23624 AN: 41440

American (AMR) AF: 0.123 AC: 1884 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0686 AC: 238 AN: 3468

East Asian (EAS) AF: 0.0494 AC: 256 AN: 5180

South Asian (SAS) AF: 0.0536 AC: 258 AN: 4812

European-Finnish (FIN) AF: 0.0756 AC: 800 AN: 10588

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0710 AC: 4830 AN: 67986

Other (OTH) AF: 0.158 AC: 332 AN: 2104

Alfa AF: 0.112 Hom.: 3070

Bravo AF: 0.232

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.51
PhyloP100		-2.1
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: rs10851420; hg19: chr15-45385916;