dbSNP rs28559568: DUOXA2:c.148-30C>T (chr15-45115769-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.148-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,613,992 control chromosomes in the GnomAD database, including 492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.032 ( 133 hom., cov: 32)

Exomes 𝑓: 0.015 ( 359 hom. )

Consequence

DUOXA2
NM_207581.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.325

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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 15-45115769-C-T is Benign according to our data. Variant chr15-45115769-C-T is described in ClinVar as [Benign]. Clinvar id is 1270124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUOXA2	NM_207581.4 link	c.148-30C>T		intron_variant	Intron 1 of 5	ENST00000323030.6	NP_997464.2	Q1HG44-1
DUOXA2	XM_017022180.2 link	c.148-30C>T		intron_variant	Intron 1 of 5		XP_016877669.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DUOXA2	ENST00000323030.6 link	c.148-30C>T	intron_variant	Intron 1 of 5	1	NM_207581.4	ENSP00000319705.5	Q1HG44-1
DUOXA2	ENST00000491993.2 link	n.*185C>T	non_coding_transcript_exon_variant	Exon 2 of 6	1		ENSP00000454110.1	Q1HG44-2
DUOXA2	ENST00000491993.2 link	n.*185C>T	3_prime_UTR_variant	Exon 2 of 6	1		ENSP00000454110.1	Q1HG44-2
DUOXA2	ENST00000350243.10 link	n.428-30C>T	intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.0316

AC:

4801

AN:

152082

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0694

Gnomad AMI

AF:

0.0582

Gnomad AMR

AF:

0.0326

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.0663

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.0302

GnomAD3 exomes

AF:

0.0245

AC:

6127

AN:

249842

Hom.:

162

AF XY:

0.0224

AC XY:

3035

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.0725

Gnomad AMR exome

AF:

0.0451

Gnomad ASJ exome

AF:

0.00796

Gnomad EAS exome

AF:

0.0690

Gnomad SAS exome

AF:

0.0161

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.0111

Gnomad OTH exome

AF:

0.0206

GnomAD4 exome

AF:

0.0147

AC:

21523

AN:

1461792

Hom.:

359

Cov.:

AF XY:

0.0144

AC XY:

10499

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0719

Gnomad4 AMR exome

AF:

0.0425

Gnomad4 ASJ exome

AF:

0.00826

Gnomad4 EAS exome

AF:

0.0677

Gnomad4 SAS exome

AF:

0.0154

Gnomad4 FIN exome

AF:

0.0108

Gnomad4 NFE exome

AF:

0.0101

Gnomad4 OTH exome

AF:

0.0193

GnomAD4 genome

AF:

0.0317

AC:

4818

AN:

152200

Hom.:

133

Cov.:

AF XY:

0.0318

AC XY:

2370

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0695

Gnomad4 AMR

AF:

0.0326

Gnomad4 ASJ

AF:

0.0109

Gnomad4 EAS

AF:

0.0658

Gnomad4 SAS

AF:

0.0148

Gnomad4 FIN

AF:

0.0136

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.0309

Alfa

AF:

0.0173

Hom.:

Bravo

AF:

0.0360

Asia WGS

AF:

0.0800

AC:

278

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.80

BranchPoint Hunter

0.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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