Variant 15-45116512-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_207581.4(DUOXA2):c.341-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 1,613,584 control chromosomes in the GnomAD database, including 790,660 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 67845 hom., cov: 33)

Exomes 𝑓: 0.99 ( 722815 hom. )

Consequence

DUOXA2
NM_207581.4 splice_region, intron

Scores

Splicing: ADA: 0.0002449

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.380

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 15-45116512-A-G is Benign according to our data. Variant chr15-45116512-A-G is described in ClinVar as [Benign]. Clinvar id is 263304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45116512-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.341-4A>G		splice_region_variant, intron_variant		ENST00000323030.6	NP_997464.2	Q1HG44-1
DUOXA2	XM_017022180.2 linkuse as main transcript	c.388A>G	p.Thr130Ala	missense_variant	4/6		XP_016877669.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DUOXA2	ENST00000323030.6 linkuse as main transcript	c.341-4A>G	splice_region_variant, intron_variant	1	NM_207581.4	ENSP00000319705.5	Q1HG44-1
DUOXA2	ENST00000491993.2 linkuse as main transcript	n.*408-4A>G	splice_region_variant, intron_variant	1		ENSP00000454110.1	Q1HG44-2
DUOXA2	ENST00000350243.10 linkuse as main transcript	n.621-4A>G	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.939

AC:

142920

AN:

152158

Hom.:

67809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.787

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.981

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.962

GnomAD3 exomes

AF:

0.985

AC:

245352

AN:

248988

Hom.:

121207

AF XY:

0.989

AC XY:

133743

AN XY:

135212

show subpopulations

Gnomad AFR exome

AF:

0.787

Gnomad AMR exome

AF:

0.992

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.995

GnomAD4 exome

AF:

0.994

AC:

1452648

AN:

1461308

Hom.:

722815

Cov.:

AF XY:

0.995

AC XY:

723338

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.788

Gnomad4 AMR exome

AF:

0.991

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.988

GnomAD4 genome

AF:

0.939

AC:

143016

AN:

152276

Hom.:

67845

Cov.:

AF XY:

0.943

AC XY:

70190

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.787

Gnomad4 AMR

AF:

0.981

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.963

Alfa

AF:

0.989

Hom.:

48597

Bravo

AF:

0.932

Asia WGS

AF:

0.987

AC:

3433

AN:

3478

EpiCase

AF:

0.999

EpiControl

AF:

0.999

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Thyroglobulin synthesis defect

Benign:1

Benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.4

DANN

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00024

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.070

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