Genetic Variant NM_207581.4:c.147+94C>A (chr15-45114846-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUOXA2	NM_207581.4 link	c.147+94C>A		intron_variant	Intron 1 of 5	ENST00000323030.6	NP_997464.2	Q1HG44-1
DUOXA2	XM_017022180.2 link	c.147+94C>A		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.147+94C>A	intron_variant	Intron 1 of 5	1	NM_207581.4	ENSP00000319705.5	Q1HG44-1
DUOXA2	ENST00000491993.2 link	n.147+94C>A	intron_variant	Intron 1 of 5	1		ENSP00000454110.1	Q1HG44-2
DUOXA2	ENST00000350243.10 link	n.427+94C>A	intron_variant	Intron 1 of 4	2

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

Gnomad4 AFR exome

AF:

0.0806

Gnomad4 AMR exome

AF:

0.00344

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000824

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000537

Gnomad4 OTH exome

AF:

0.00421

GnomAD4 genome

AF:

0.0223

AC:

3388

AN:

152222

Hom.:

134

Cov.:

AF XY:

0.0206

AC XY:

1533

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0779

Gnomad4 AMR

AF:

0.00706

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.0261

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 05, 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

-0.80

CADD

Benign

5.1

DANN

Benign

0.71

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