rs269869

Variant names:

• chr15-45099368-A-T
• rs269869
• NM_001363711.2:c.3515+15T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-45099368-A-T
• chr15-45099368-A-C
• chr15-45099368-A-G

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.3515+15T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,612,502 control chromosomes in the GnomAD database, including 804,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (75080 hom., cov: 31)
  • Exomes 𝑓: 1.0 (729205 hom.)
• Consequence: DUOX2 NM_001363711.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.749
• Publications: 6 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=-0.73).
• BP6: Variant 15-45099368-A-T is Benign according to our data. Variant chr15-45099368-A-T is described in ClinVar as Benign. ClinVar VariationId is 260324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 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.3515+15T>A		intron	N/A	NP_001350640.1	X6RAN8
	DUOX2	NM_014080.5		c.3515+15T>A		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.3515+15T>A		intron	N/A	ENSP00000373691.7	X6RAN8
	DUOX2	ENST00000603300.1	TSL:1	c.3515+15T>A		intron	N/A	ENSP00000475084.1	Q9NRD8
	DUOX2	ENST00000558383.1	TSL:5	n.6302T>A		non_coding_transcript_exon	Exon 17 of 17

Frequencies

GnomAD3 genomes AF: 0.993 AC: 151075 AN: 152128 Hom.: 75025 Cov.: 31

Gnomad AFR AF: 0.976

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.993

GnomAD2 exomes AF: 0.998 AC: 250786 AN: 251232 AF XY: 0.999

Gnomad AFR exome AF: 0.974

Gnomad AMR exome AF: 0.999

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.999

GnomAD4 exome AF: 0.999 AC: 1459318 AN: 1460256 Hom.: 729205 Cov.: 34 AF XY: 0.999 AC XY: 726198 AN XY: 726606

African (AFR) AF: 0.976 AC: 32642 AN: 33442

American (AMR) AF: 0.999 AC: 44687 AN: 44716

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26130 AN: 26130

East Asian (EAS) AF: 1.00 AC: 39690 AN: 39690

South Asian (SAS) AF: 1.00 AC: 86210 AN: 86214

European-Finnish (FIN) AF: 1.00 AC: 53360 AN: 53360

Middle Eastern (MID) AF: 0.999 AC: 5749 AN: 5752

European-Non Finnish (NFE) AF: 1.00 AC: 1110623 AN: 1110636

Other (OTH) AF: 0.999 AC: 60227 AN: 60316

GnomAD4 genome AF: 0.993 AC: 151189 AN: 152246 Hom.: 75080 Cov.: 31 AF XY: 0.993 AC XY: 73950 AN XY: 74438

African (AFR) AF: 0.976 AC: 40511 AN: 41528

American (AMR) AF: 0.999 AC: 15278 AN: 15300

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5172 AN: 5172

South Asian (SAS) AF: 1.00 AC: 4822 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10610 AN: 10610

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68016 AN: 68020

Other (OTH) AF: 0.993 AC: 2102 AN: 2116

Alfa AF: 0.997 Hom.: 13885

Bravo AF: 0.992

Asia WGS AF: 0.998 AC: 3471 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Thyroid dyshormonogenesis 6 (3)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.8
DANN	Benign	0.76
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs269869; hg19: chr15-45391566;