rs2576090

Positions:

• chr15-45116216-C-A
• chr15-45116216-C-G
• chr15-45116216-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207581.4(DUOXA2):​c.298C>A​(p.Arg100Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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)
• Consequence: DUOXA2 NM_207581.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.48

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2580701).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOXA2	NM_207581.4	c.298C>A	p.Arg100Ser	missense_variant	3/6	ENST00000323030.6	NP_997464.2
DUOXA2	XM_017022180.2	c.298C>A	p.Arg100Ser	missense_variant	3/6		XP_016877669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUOXA2	ENST00000323030.6	c.298C>A	p.Arg100Ser	missense_variant	3/6	1	NM_207581.4	ENSP00000319705.5
DUOXA2	ENST00000491993.2	n.*365C>A		non_coding_transcript_exon_variant	3/6	1		ENSP00000454110.1
DUOXA2	ENST00000491993.2	n.*365C>A		3_prime_UTR_variant	3/6	1		ENSP00000454110.1
DUOXA2	ENST00000350243.10	n.578C>A		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.010	D
Polyphen		0.0070	B
Vest4		0.21
MutPred		0.57		Loss of methylation at R100 (P = 0.0168);
MVP		0.37
MPC		0.20
ClinPred		0.91	D
GERP RS		5.4
Varity_R		0.39
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2576090; hg19: chr15-45408414;