rs398093

Variant names:

• chr4-107059393-C-T
• rs398093
• ENST00000513208.5:c.-79+129034G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000513208.5(DKK2):​c.-79+129034G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,112 control chromosomes in the GnomAD database, including 1,540 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1540 hom., cov: 32)
• Consequence: DKK2 ENST00000513208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 2 publications found

Genes affected

DKK2 (HGNC:2892): (dickkopf WNT signaling pathway inhibitor 2) This gene encodes a protein that is a member of the dickkopf family. The secreted protein contains two cysteine rich regions and is involved in embryonic development through its interactions with the Wnt signaling pathway. It can act as either an agonist or antagonist of Wnt/beta-catenin signaling, depending on the cellular context and the presence of the co-factor kremen 2. Activity of this protein is also modulated by binding to the Wnt co-receptor LDL-receptor related protein 6 (LRP6). [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DKK2	ENST00000513208.5	c.-79+129034G>A		intron_variant	Intron 2 of 4	1		ENSP00000421255.1
DKK2	ENST00000510463.1	c.84+68549G>A		intron_variant	Intron 3 of 5	3		ENSP00000423797.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20810 AN: 151994 Hom.: 1538 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.151

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.137 AC: 20812 AN: 152112 Hom.: 1540 Cov.: 32 AF XY: 0.134 AC XY: 9977 AN XY: 74340

African (AFR) AF: 0.169 AC: 7030 AN: 41530

American (AMR) AF: 0.124 AC: 1893 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 595 AN: 3470

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5176

South Asian (SAS) AF: 0.131 AC: 633 AN: 4820

European-Finnish (FIN) AF: 0.128 AC: 1353 AN: 10562

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.129 AC: 8779 AN: 67974

Other (OTH) AF: 0.149 AC: 313 AN: 2104

Alfa AF: 0.135 Hom.: 2328

Bravo AF: 0.139

Asia WGS AF: 0.0800 AC: 278 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.38
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs398093; hg19: chr4-107980550;