15-45093298-A-T

Variant names:

• chr15-45093298-A-T
• rs4775744
• NM_001363711.2:c.*852T>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.*852T>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 0.224 in 152,118 control chromosomes in the GnomAD database, including 7,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (7463 hom., cov: 32)
  • Exomes 𝑓: 0.073 (1 hom.)
• Consequence: DUOX2 NM_001363711.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.196
• 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=-0.92).
• BP6: Variant 15-45093298-A-T is Benign according to our data. Variant chr15-45093298-A-T is described in ClinVar as Benign. ClinVar VariationId is 316125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 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.*852T>A		3_prime_UTR	Exon 34 of 34	NP_001350640.1	X6RAN8
	DUOX2	NM_014080.5		c.*852T>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.*852T>A		3_prime_UTR	Exon 34 of 34	ENSP00000373691.7	X6RAN8
	DUOX2	ENST00000603300.1	TSL:1	c.*852T>A		3_prime_UTR	Exon 34 of 34	ENSP00000475084.1	Q9NRD8

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33919 AN: 151904 Hom.: 7436 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0848

Gnomad EAS AF: 0.0492

Gnomad SAS AF: 0.0583

Gnomad FIN AF: 0.0766

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0882

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.0729 AC: 7 AN: 96 Hom.: 1 Cov.: 0 AF XY: 0.0968 AC XY: 6 AN XY: 62

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0366 AC: 3 AN: 82

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.224 AC: 34002 AN: 152022 Hom.: 7463 Cov.: 32 AF XY: 0.217 AC XY: 16124 AN XY: 74346

African (AFR) AF: 0.573 AC: 23720 AN: 41402

American (AMR) AF: 0.141 AC: 2153 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0848 AC: 294 AN: 3466

East Asian (EAS) AF: 0.0491 AC: 254 AN: 5172

South Asian (SAS) AF: 0.0583 AC: 281 AN: 4818

European-Finnish (FIN) AF: 0.0766 AC: 812 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0883 AC: 6001 AN: 67976

Other (OTH) AF: 0.173 AC: 365 AN: 2112

Alfa AF: 0.0520 Hom.: 69

Bravo AF: 0.244

Asia WGS AF: 0.125 AC: 434 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.92
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-0.20
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: rs4775744; hg19: chr15-45385496;