chr15-45093672-C-A

Variant names:

• chr15-45093672-C-A
• rs12324044
• NM_001363711.2:c.*478G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001363711.2(DUOX2):​c.*478G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DUOX2 NM_001363711.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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.*478G>T		3_prime_UTR	Exon 34 of 34	NP_001350640.1	X6RAN8
	DUOX2	NM_014080.5		c.*478G>T		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.*478G>T		3_prime_UTR	Exon 34 of 34	ENSP00000373691.7	X6RAN8
	DUOX2	ENST00000603300.1	TSL:1	c.*478G>T		3_prime_UTR	Exon 34 of 34	ENSP00000475084.1	Q9NRD8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 28804 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 15286

African (AFR) AF: 0.00 AC: 0 AN: 1352

American (AMR) AF: 0.00 AC: 0 AN: 2918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 624

East Asian (EAS) AF: 0.00 AC: 0 AN: 2012

South Asian (SAS) AF: 0.00 AC: 0 AN: 2850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 104

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 16736

Other (OTH) AF: 0.00 AC: 0 AN: 1368

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.70
DANN	Benign	0.45
PhyloP100		-0.75

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: rs12324044; hg19: chr15-45385870;