dbSNP rs75156596: DUOXA2:c.147+94C>A (chr15-45114846-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_207581.4(DUOXA2):c.147+94C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,576,622 control chromosomes in the GnomAD database, including 255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 134 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 121 hom. )

Consequence

DUOXA2
NM_207581.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.182

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

thyroid dyshormonogenesis 5
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
familial thyroid dyshormonogenesis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DUOXA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 15-45114846-C-A is Benign according to our data. Variant chr15-45114846-C-A is described in ClinVar as Benign. ClinVar VariationId is 1268347.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0757 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207581.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUOXA2	NM_207581.4	MANE Select	c.147+94C>A		intron	N/A	NP_997464.2	Q1HG44-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DUOXA2	ENST00000323030.6	TSL:1 MANE Select	c.147+94C>A	intron	N/A	ENSP00000319705.5	Q1HG44-1
DUOXA2	ENST00000491993.2	TSL:1	n.147+94C>A	intron	N/A	ENSP00000454110.1	Q1HG44-2
DUOXA2	ENST00000958164.1		c.147+94C>A	intron	N/A	ENSP00000628223.1

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3383

AN:

152104

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0780

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00713

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0182

GnomAD4 exome

AF:

0.00218

AC:

3102

AN:

1424400

Hom.:

121

AF XY:

0.00185

AC XY:

1313

AN XY:

710038

show subpopulations

African (AFR)

AF:

0.0806

AC:

2630

AN:

32616

American (AMR)

AF:

0.00344

AC:

153

AN:

44470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25776

East Asian (EAS)

AF:

0.00

AC:

AN:

39464

South Asian (SAS)

AF:

0.0000824

AC:

AN:

85002

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52432

Middle Eastern (MID)

AF:

0.00119

AC:

AN:

5040

European-Non Finnish (NFE)

AF:

0.0000537

AC:

AN:

1080624

Other (OTH)

AF:

0.00421

AC:

248

AN:

58976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

143

286

428

571

714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0223

AC:

3388

AN:

152222

Hom.:

134

Cov.:

AF XY:

0.0206

AC XY:

1533

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0779

AC:

3234

AN:

41504

American (AMR)

AF:

0.00706

AC:

108

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68014

Other (OTH)

AF:

0.0180

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

145

289

434

578

723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00965

Hom.:

Bravo

AF:

0.0261

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.1

(source)

DANN

Benign

0.71

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over