Variant 15-45114656-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_StrongBP7BS1BS2

The NM_207581.4(DUOXA2):c.51C>T(p.Ala17Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,614,206 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 23 hom. )

Consequence

DUOXA2
NM_207581.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.73

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=-0.67).

BP6

Variant 15-45114656-C-T is Benign according to our data. Variant chr15-45114656-C-T is described in ClinVar as [Benign]. Clinvar id is 790694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-45114656-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.73 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0012 (1747/1461878) while in subpopulation AMR AF= 0.0178 (795/44722). AF 95% confidence interval is 0.0168. There are 23 homozygotes in gnomad4_exome. There are 790 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOXA2	NM_207581.4 linkuse as main transcript	c.51C>T	p.Ala17Ala	synonymous_variant	1/6	ENST00000323030.6	NP_997464.2	Q1HG44-1
DUOXA2	XM_017022180.2 linkuse as main transcript	c.51C>T	p.Ala17Ala	synonymous_variant	1/6		XP_016877669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DUOXA2	ENST00000323030.6 linkuse as main transcript	c.51C>T	p.Ala17Ala	synonymous_variant	1/6	1	NM_207581.4	ENSP00000319705.5	Q1HG44-1
DUOXA2	ENST00000491993.2 linkuse as main transcript	n.51C>T		non_coding_transcript_exon_variant	1/6	1		ENSP00000454110.1	Q1HG44-2
DUOXA2	ENST00000350243.10 linkuse as main transcript	n.331C>T		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.00170

AC:

259

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00558

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00649

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00415

AC:

1042

AN:

251320

Hom.:

AF XY:

0.00327

AC XY:

444

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000801

Gnomad AMR exome

AF:

0.0210

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00353

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00467

Gnomad NFE exome

AF:

0.000651

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00120

AC:

1747

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

790

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.0178

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00406

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.00500

Gnomad4 NFE exome

AF:

0.000274

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00174

AC:

265

AN:

152328

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00560

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00649

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.000777

Hom.:

Bravo

AF:

0.00206

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000415

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	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.20

DANN

Benign

0.92

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