Genetic Variant DUOXA2:c.555-18C>T (chr15-45117073-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.555-18C>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 1,596,472 control chromosomes in the GnomAD database, including 618,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 45200 hom., cov: 36)

Exomes 𝑓: 0.88 ( 573597 hom. )

Consequence

DUOXA2
NM_207581.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

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:

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=-0.91).

BP6

Variant 15-45117073-C-T is Benign according to our data. Variant chr15-45117073-C-T is described in ClinVar as [Benign]. Clinvar id is 263306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45117073-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUOXA2	NM_207581.4 link	c.555-18C>T		intron_variant	Intron 4 of 5	ENST00000323030.6	NP_997464.2	Q1HG44-1
DUOXA2	XM_017022180.2 link	c.606-18C>T		intron_variant	Intron 4 of 5		XP_016877669.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DUOXA2	ENST00000323030.6 link	c.555-18C>T	intron_variant	Intron 4 of 5	1	NM_207581.4	ENSP00000319705.5	Q1HG44-1
DUOXA2	ENST00000491993.2 link	n.*622-18C>T	intron_variant	Intron 4 of 5	1		ENSP00000454110.1	Q1HG44-2
DUOXA2	ENST00000350243.10 link	n.1178C>T	non_coding_transcript_exon_variant	Exon 4 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.711

AC:

108226

AN:

152158

Hom.:

45213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.896

Gnomad AMR

AF:

0.834

Gnomad ASJ

AF:

0.891

Gnomad EAS

AF:

0.866

Gnomad SAS

AF:

0.910

Gnomad FIN

AF:

0.911

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.903

Gnomad OTH

AF:

0.763

GnomAD3 exomes

AF:

0.851

AC:

193876

AN:

227768

Hom.:

85740

AF XY:

0.864

AC XY:

108937

AN XY:

126054

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.852

Gnomad ASJ exome

AF:

0.898

Gnomad EAS exome

AF:

0.869

Gnomad SAS exome

AF:

0.907

Gnomad FIN exome

AF:

0.920

Gnomad NFE exome

AF:

0.905

Gnomad OTH exome

AF:

0.881

GnomAD4 exome

AF:

0.885

AC:

1277560

AN:

1444196

Hom.:

573597

Cov.:

AF XY:

0.888

AC XY:

638203

AN XY:

718848

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.846

Gnomad4 ASJ exome

AF:

0.899

Gnomad4 EAS exome

AF:

0.859

Gnomad4 SAS exome

AF:

0.908

Gnomad4 FIN exome

AF:

0.919

Gnomad4 NFE exome

AF:

0.905

Gnomad4 OTH exome

AF:

0.859

GnomAD4 genome

AF:

0.711

AC:

108211

AN:

152276

Hom.:

45200

Cov.:

AF XY:

0.720

AC XY:

53607

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.234

Gnomad4 AMR

AF:

0.834

Gnomad4 ASJ

AF:

0.891

Gnomad4 EAS

AF:

0.866

Gnomad4 SAS

AF:

0.910

Gnomad4 FIN

AF:

0.911

Gnomad4 NFE

AF:

0.903

Gnomad4 OTH

AF:

0.759

Alfa

AF:

0.815

Hom.:

9671

Bravo

AF:

0.684

Asia WGS

AF:

0.804

AC:

2798

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

not provided

Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.085

DANN

Benign

0.82

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