chr15-45114846-C-A

Position:

• chr15-45114846-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.182

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 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/exons	MANE	UniProt
DUOXA2	NM_207581.4	c.147+94C>A		intron_variant		ENST00000323030.6
DUOXA2	XM_017022180.2	c.147+94C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUOXA2	ENST00000323030.6	c.147+94C>A		intron_variant		1	NM_207581.4	P1
DUOXA2	ENST00000491993.2	c.147+94C>A		intron_variant, NMD_transcript_variant		1
DUOXA2	ENST00000350243.10	n.427+94C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3383 AN: 152104 Hom.: 134 Cov.: 32

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

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.: 32 AF XY: 0.0206 AC XY: 1533 AN XY: 74430

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.: 8

Bravo AF: 0.0261

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

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

Other links and lift over

dbSNP: rs75156596; hg19: chr15-45407044;