15-45116501-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_207581.4(DUOXA2):c.341-15C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.550

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
DUOXA2	NM_207581.4	c.341-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000323030.6
DUOXA2	XM_017022180.2	c.377C>T	p.Pro126Leu	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUOXA2	ENST00000323030.6	c.341-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_207581.4	P1
DUOXA2	ENST00000491993.2	c.*408-15C>T		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1
DUOXA2	ENST00000350243.10	n.621-15C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108005 AN: 151980 Hom.: 45122 Cov.: 33

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

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.: 50 AF XY: 0.888 AC XY: 645306 AN XY: 726778

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.: 33 AF XY: 0.719 AC XY: 53482 AN XY: 74364

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:3

Revision: criteria provided, single submitter

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

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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

Other links and lift over

dbSNP: rs2252371; hg19: chr15-45408699;