Variant 15-45116216-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207581.4(DUOXA2):c.298C>T(p.Arg100Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R100G) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DUOXA2
NM_207581.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.48

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOXA2	NM_207581.4 link	c.298C>T	p.Arg100Cys	missense_variant	3/6	ENST00000323030.6	NP_997464.2	Q1HG44-1
DUOXA2	XM_017022180.2 link	c.298C>T	p.Arg100Cys	missense_variant	3/6		XP_016877669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DUOXA2	ENST00000323030.6 link	c.298C>T	p.Arg100Cys	missense_variant	3/6	1	NM_207581.4	ENSP00000319705.5	Q1HG44-1
DUOXA2	ENST00000491993.2 link	n.*365C>T		non_coding_transcript_exon_variant	3/6	1		ENSP00000454110.1	Q1HG44-2
DUOXA2	ENST00000491993.2 link	n.*365C>T		3_prime_UTR_variant	3/6	1		ENSP00000454110.1	Q1HG44-2
DUOXA2	ENST00000350243.10 link	n.578C>T		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.081

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.096

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.083

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.94

REVEL

Benign

0.27

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.79

Vest4

0.36

MutPred

0.72

Loss of MoRF binding (P = 0.0109);

MVP

0.37

MPC

0.25

ClinPred

0.80

GERP RS

5.4

Varity_R

0.31

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over