Variant 15-45111769-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000389039.11(DUOX2):c.512T>G(p.Leu171Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,612 control chromosomes in the GnomAD database, with no homozygous occurrence. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. L171P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 28)

Consequence

DUOX2
ENST00000389039.11 missense, splice_region

Scores

Splicing: ADA: 0.0003080

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.59

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOX2	NM_001363711.2 linkuse as main transcript	c.512T>G	p.Leu171Arg	missense_variant, splice_region_variant	5/34	ENST00000389039.11	NP_001350640.1
DUOX2	NM_014080.5 linkuse as main transcript	c.512T>G	p.Leu171Arg	missense_variant, splice_region_variant	5/34		NP_054799.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DUOX2	ENST00000389039.11 linkuse as main transcript	c.512T>G	p.Leu171Arg	missense_variant, splice_region_variant	5/34	1	NM_001363711.2	ENSP00000373691	P4
DUOX2	ENST00000603300.1 linkuse as main transcript	c.512T>G	p.Leu171Arg	missense_variant, splice_region_variant	5/34	1		ENSP00000475084	A1
DUOX2	ENST00000558383.1 linkuse as main transcript	n.555T>G		non_coding_transcript_exon_variant	4/17	5

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151612

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151612

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74056

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.0083

T;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.072

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.9

.;L

MutationTaster

Benign

0.56

PrimateAI

Benign

0.45

PROVEAN

Benign

1.3

N;.

REVEL

Benign

0.22

Sift

Benign

0.82

T;.

Sift4G

Benign

0.67

T;T

Polyphen

0.17

.;B

Vest4

0.69

MutPred

0.57

Gain of disorder (P = 0.017);Gain of disorder (P = 0.017);

MVP

0.63

MPC

1.2

ClinPred

0.25

GERP RS

1.1

Varity_R

0.14

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00031

dbscSNV1_RF

Benign

0.0020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over