Variant 15-45116493-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_207581.4(DUOXA2):c.341-23C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 1,612,674 control chromosomes in the GnomAD database, including 654,414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.77 ( 49171 hom., cov: 33)

Exomes 𝑓: 0.91 ( 605243 hom. )

Consequence

DUOXA2
NM_207581.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.18

Variant links:

Genes affected

DUOXA2 (HGNC:32698): (dual oxidase maturation factor 2) This gene encodes an endoplasmic reticulum protein that is necessary for proper cellular localization and maturation of functional dual oxidase 2. Mutations in this gene have been associated with thyroid dyshormonogenesis 5.[provided by RefSeq, Feb 2010]

DUOXA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-45116493-C-G is Benign according to our data. Variant chr15-45116493-C-G is described in ClinVar as [Benign]. Clinvar id is 1243924.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUOXA2	NM_207581.4 linkuse as main transcript	c.341-23C>G		intron_variant		ENST00000323030.6
DUOXA2	XM_017022180.2 linkuse as main transcript	c.369C>G	p.Pro123=	synonymous_variant	4/6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
DUOXA2	ENST00000323030.6 linkuse as main transcript	c.341-23C>G	intron_variant	1	NM_207581.4	P1	Q1HG44-1
DUOXA2	ENST00000491993.2 linkuse as main transcript	c.*408-23C>G	intron_variant, NMD_transcript_variant	1			Q1HG44-2
DUOXA2	ENST00000350243.10 linkuse as main transcript	n.621-23C>G	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.770

AC:

117081

AN:

151964

Hom.:

49176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.401

Gnomad AMI

AF:

0.896

Gnomad AMR

AF:

0.857

Gnomad ASJ

AF:

0.914

Gnomad EAS

AF:

0.938

Gnomad SAS

AF:

0.934

Gnomad FIN

AF:

0.915

Gnomad MID

AF:

0.860

Gnomad NFE

AF:

0.918

Gnomad OTH

AF:

0.808

GnomAD3 exomes

AF:

0.882

AC:

218730

AN:

248034

Hom.:

98643

AF XY:

0.891

AC XY:

120136

AN XY:

134772

show subpopulations

Gnomad AFR exome

AF:

0.389

Gnomad AMR exome

AF:

0.865

Gnomad ASJ exome

AF:

0.916

Gnomad EAS exome

AF:

0.942

Gnomad SAS exome

AF:

0.930

Gnomad FIN exome

AF:

0.924

Gnomad NFE exome

AF:

0.919

Gnomad OTH exome

AF:

0.904

GnomAD4 exome

AF:

0.906

AC:

1323924

AN:

1460592

Hom.:

605243

Cov.:

AF XY:

0.909

AC XY:

660464

AN XY:

726624

show subpopulations

Gnomad4 AFR exome

AF:

0.388

Gnomad4 AMR exome

AF:

0.861

Gnomad4 ASJ exome

AF:

0.918

Gnomad4 EAS exome

AF:

0.935

Gnomad4 SAS exome

AF:

0.930

Gnomad4 FIN exome

AF:

0.925

Gnomad4 NFE exome

AF:

0.921

Gnomad4 OTH exome

AF:

0.890

GnomAD4 genome

AF:

0.770

AC:

117103

AN:

152082

Hom.:

49171

Cov.:

AF XY:

0.777

AC XY:

57777

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.400

Gnomad4 AMR

AF:

0.857

Gnomad4 ASJ

AF:

0.914

Gnomad4 EAS

AF:

0.938

Gnomad4 SAS

AF:

0.934

Gnomad4 FIN

AF:

0.915

Gnomad4 NFE

AF:

0.918

Gnomad4 OTH

AF:

0.807

Alfa

AF:

0.839

Hom.:

6580

Bravo

AF:

0.750

Asia WGS

AF:

0.879

AC:

3059

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.9

DANN

Benign

0.71

BranchPoint Hunter

0.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over