15-45115769-C-T

Position:

• chr15-45115769-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.148-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,613,992 control chromosomes in the GnomAD database, including 492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.032 (133 hom., cov: 32)
  • Exomes 𝑓: 0.015 (359 hom.)
• Consequence: DUOXA2 NM_207581.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.325

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: This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 15-45115769-C-T is Benign according to our data. Variant chr15-45115769-C-T is described in ClinVar as [Benign]. Clinvar id is 1270124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOXA2	NM_207581.4	c.148-30C>T		intron_variant		ENST00000323030.6	NP_997464.2
DUOXA2	XM_017022180.2	c.148-30C>T		intron_variant			XP_016877669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUOXA2	ENST00000323030.6	c.148-30C>T		intron_variant		1	NM_207581.4	ENSP00000319705.5
DUOXA2	ENST00000491993.2	n.*185C>T		non_coding_transcript_exon_variant	2/6	1		ENSP00000454110.1
DUOXA2	ENST00000491993.2	n.*185C>T		3_prime_UTR_variant	2/6	1		ENSP00000454110.1
DUOXA2	ENST00000350243.10	n.428-30C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4801 AN: 152082 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.0663

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0302

GnomAD3 exomes AF: 0.0245 AC: 6127 AN: 249842 Hom.: 162 AF XY: 0.0224 AC XY: 3035 AN XY: 135632

Gnomad AFR exome AF: 0.0725

Gnomad AMR exome AF: 0.0451

Gnomad ASJ exome AF: 0.00796

Gnomad EAS exome AF: 0.0690

Gnomad SAS exome AF: 0.0161

Gnomad FIN exome AF: 0.0103

Gnomad NFE exome AF: 0.0111

Gnomad OTH exome AF: 0.0206

GnomAD4 exome AF: 0.0147 AC: 21523 AN: 1461792 Hom.: 359 Cov.: 32 AF XY: 0.0144 AC XY: 10499 AN XY: 727206

Gnomad4 AFR exome AF: 0.0719

Gnomad4 AMR exome AF: 0.0425

Gnomad4 ASJ exome AF: 0.00826

Gnomad4 EAS exome AF: 0.0677

Gnomad4 SAS exome AF: 0.0154

Gnomad4 FIN exome AF: 0.0108

Gnomad4 NFE exome AF: 0.0101

Gnomad4 OTH exome AF: 0.0193

GnomAD4 genome AF: 0.0317 AC: 4818 AN: 152200 Hom.: 133 Cov.: 32 AF XY: 0.0318 AC XY: 2370 AN XY: 74412

Gnomad4 AFR AF: 0.0695

Gnomad4 AMR AF: 0.0326

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.0658

Gnomad4 SAS AF: 0.0148

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.0309

Alfa AF: 0.0173 Hom.: 21

Bravo AF: 0.0360

Asia WGS AF: 0.0800 AC: 278 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	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.80
BranchPoint Hunter		0.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs28559568; hg19: chr15-45407967;