Variant 15-45117274-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_207581.4(DUOXA2):c.738C>T(p.Tyr246Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,603,938 control chromosomes in the GnomAD database, including 223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 28 hom., cov: 33)

Exomes 𝑓: 0.011 ( 195 hom. )

Consequence

DUOXA2
NM_207581.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.77

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:

DUOXA2 (HGNC:):

DUOXA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 15-45117274-C-T is Benign according to our data. Variant chr15-45117274-C-T is described in ClinVar as [Benign]. Clinvar id is 1293942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45117274-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.77 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOXA2	NM_207581.4 linkuse as main transcript	c.738C>T	p.Tyr246Tyr	synonymous_variant	5/6	ENST00000323030.6	NP_997464.2	Q1HG44-1
DUOXA2	XM_017022180.2 linkuse as main transcript	c.789C>T	p.Tyr263Tyr	synonymous_variant	5/6		XP_016877669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DUOXA2	ENST00000323030.6 linkuse as main transcript	c.738C>T	p.Tyr246Tyr	synonymous_variant	5/6	1	NM_207581.4	ENSP00000319705.5	Q1HG44-1
DUOXA2	ENST00000491993.2 linkuse as main transcript	n.*805C>T		non_coding_transcript_exon_variant	5/6	1		ENSP00000454110.1	Q1HG44-2
DUOXA2	ENST00000491993.2 linkuse as main transcript	n.*805C>T		3_prime_UTR_variant	5/6	1		ENSP00000454110.1	Q1HG44-2
DUOXA2	ENST00000350243.10 linkuse as main transcript	n.1379C>T		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1936

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.0582

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.0565

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00916

Gnomad OTH

AF:

0.0138

GnomAD3 exomes

AF:

0.0169

AC:

4019

AN:

237622

Hom.:

AF XY:

0.0154

AC XY:

1998

AN XY:

129994

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.0378

Gnomad ASJ exome

AF:

0.00280

Gnomad EAS exome

AF:

0.0539

Gnomad SAS exome

AF:

0.00820

Gnomad FIN exome

AF:

0.00883

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.0141

GnomAD4 exome

AF:

0.0111

AC:

16121

AN:

1451584

Hom.:

195

Cov.:

AF XY:

0.0108

AC XY:

7797

AN XY:

720750

show subpopulations

Gnomad4 AFR exome

AF:

0.0107

Gnomad4 AMR exome

AF:

0.0345

Gnomad4 ASJ exome

AF:

0.00278

Gnomad4 EAS exome

AF:

0.0617

Gnomad4 SAS exome

AF:

0.00759

Gnomad4 FIN exome

AF:

0.00971

Gnomad4 NFE exome

AF:

0.00889

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

AF:

0.0128

AC:

1945

AN:

152354

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

978

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.0204

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.0561

Gnomad4 SAS

AF:

0.00870

Gnomad4 FIN

AF:

0.0121

Gnomad4 NFE

AF:

0.00916

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.00911

Hom.:

Bravo

AF:

0.0139

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.63

CADD

Benign

0.34

DANN

Benign

0.85

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

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