Genetic Variant DUOXA2:c.341-15C>T (chr15-45116501-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_207581.4(DUOXA2):c.341-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 1,613,064 control chromosomes in the GnomAD database, including 625,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 45109 hom., cov: 33)

Exomes 𝑓: 0.88 ( 580524 hom. )

Consequence

DUOXA2
NM_207581.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.550

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-45116501-C-T is Benign according to our data. Variant chr15-45116501-C-T is described in ClinVar as [Benign]. Clinvar id is 263303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45116501-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUOXA2	NM_207581.4 link	c.341-15C>T		intron_variant	Intron 3 of 5	ENST00000323030.6	NP_997464.2	Q1HG44-1
DUOXA2	XM_017022180.2 link	c.377C>T	p.Pro126Leu	missense_variant	Exon 4 of 6		XP_016877669.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DUOXA2	ENST00000323030.6 link	c.341-15C>T	intron_variant	Intron 3 of 5	1	NM_207581.4	ENSP00000319705.5	Q1HG44-1
DUOXA2	ENST00000491993.2 link	n.*408-15C>T	intron_variant	Intron 3 of 5	1		ENSP00000454110.1	Q1HG44-2
DUOXA2	ENST00000350243.10 link	n.621-15C>T	intron_variant	Intron 3 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.711

AC:

108005

AN:

151980

Hom.:

45122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.896

Gnomad AMR

AF:

0.833

Gnomad ASJ

AF:

0.893

Gnomad EAS

AF:

0.874

Gnomad SAS

AF:

0.909

Gnomad FIN

AF:

0.911

Gnomad MID

AF:

0.841

Gnomad NFE

AF:

0.902

Gnomad OTH

AF:

0.760

GnomAD3 exomes

AF:

0.853

AC:

211951

AN:

248430

Hom.:

93928

AF XY:

0.865

AC XY:

116767

AN XY:

134938

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.850

Gnomad ASJ exome

AF:

0.900

Gnomad EAS exome

AF:

0.874

Gnomad SAS exome

AF:

0.906

Gnomad FIN exome

AF:

0.920

Gnomad NFE exome

AF:

0.905

Gnomad OTH exome

AF:

0.879

GnomAD4 exome

AF:

0.885

AC:

1292681

AN:

1460966

Hom.:

580524

Cov.:

AF XY:

0.888

AC XY:

645306

AN XY:

726778

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.845

Gnomad4 ASJ exome

AF:

0.900

Gnomad4 EAS exome

AF:

0.865

Gnomad4 SAS exome

AF:

0.908

Gnomad4 FIN exome

AF:

0.919

Gnomad4 NFE exome

AF:

0.905

Gnomad4 OTH exome

AF:

0.858

GnomAD4 genome

AF:

0.710

AC:

107991

AN:

152098

Hom.:

45109

Cov.:

AF XY:

0.719

AC XY:

53482

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.833

Gnomad4 ASJ

AF:

0.893

Gnomad4 EAS

AF:

0.874

Gnomad4 SAS

AF:

0.908

Gnomad4 FIN

AF:

0.911

Gnomad4 NFE

AF:

0.902

Gnomad4 OTH

AF:

0.756

Alfa

AF:

0.864

Hom.:

43630

Bravo

AF:

0.683

Asia WGS

AF:

0.804

AC:

2798

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Thyroglobulin synthesis defect

Benign:1

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.8

DANN

Benign

0.87

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