15-45114520-C-T

Position:

• chr15-45114520-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_207581.4(DUOXA2):​c.-86C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 1,574,710 control chromosomes in the GnomAD database, including 8,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (555 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8099 hom.)
• Consequence: DUOXA2 NM_207581.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.573

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 15-45114520-C-T is Benign according to our data. Variant chr15-45114520-C-T is described in ClinVar as [Benign]. Clinvar id is 1266385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOXA2	NM_207581.4	c.-86C>T		5_prime_UTR_variant	1/6	ENST00000323030.6	NP_997464.2
DUOXA2	XM_017022180.2	c.-86C>T		5_prime_UTR_variant	1/6		XP_016877669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUOXA2	ENST00000323030	c.-86C>T		5_prime_UTR_variant	1/6	1	NM_207581.4	ENSP00000319705.5
DUOXA2	ENST00000491993.2	n.-86C>T		non_coding_transcript_exon_variant	1/6	1		ENSP00000454110.1
DUOXA2	ENST00000491993.2	n.-86C>T		5_prime_UTR_variant	1/6	1		ENSP00000454110.1
DUOXA2	ENST00000350243.10	n.195C>T		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11136 AN: 152158 Hom.: 555 Cov.: 32

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0602

GnomAD4 exome AF: 0.100 AC: 142182 AN: 1422434 Hom.: 8099 Cov.: 28 AF XY: 0.0979 AC XY: 69203 AN XY: 706870

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.0423

Gnomad4 ASJ exome AF: 0.0308

Gnomad4 EAS exome AF: 0.000340

Gnomad4 SAS exome AF: 0.0262

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.0889

GnomAD4 genome AF: 0.0731 AC: 11132 AN: 152276 Hom.: 555 Cov.: 32 AF XY: 0.0716 AC XY: 5330 AN XY: 74462

Gnomad4 AFR AF: 0.0191

Gnomad4 AMR AF: 0.0582

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.0596

Alfa AF: 0.0772 Hom.: 201

Bravo AF: 0.0657

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.9
DANN	Benign	0.81

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

Other links and lift over

dbSNP: rs187290; hg19: chr15-45406718;