chr15-45111501-C-A

Position:

• chr15-45111501-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001363711.2(DUOX2):​c.598G>T​(p.Gly200Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,399,544 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G200R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: DUOX2 NM_001363711.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOX2	NM_001363711.2	c.598G>T	p.Gly200Trp	missense_variant	6/34	ENST00000389039.11	NP_001350640.1
DUOX2	NM_014080.5	c.598G>T	p.Gly200Trp	missense_variant	6/34		NP_054799.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUOX2	ENST00000389039.11	c.598G>T	p.Gly200Trp	missense_variant	6/34	1	NM_001363711.2	ENSP00000373691.7
DUOX2	ENST00000603300.1	c.598G>T	p.Gly200Trp	missense_variant	6/34	1		ENSP00000475084.1
DUOX2	ENST00000558383.1	n.823G>T		non_coding_transcript_exon_variant	4/17	5

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD3 exomes AF: 0.00000671 AC: 1 AN: 149026 Hom.: 0 AF XY: 0.0000123 AC XY: 1 AN XY: 81352

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000229 AC: 32 AN: 1399544 Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 19 AN XY: 691150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000286

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.0045	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;D
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Uncertain	-0.070	T
MutationAssessor	Uncertain	2.8	.;M
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-4.5	D;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	.;D
Vest4		0.52
MutPred		0.67		Loss of disorder (P = 0.0115);Loss of disorder (P = 0.0115);
MVP		0.76
MPC		1.3
ClinPred		0.90	D
GERP RS		3.2
Varity_R		0.78
gMVP		0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2467827; hg19: chr15-45403699;