chr4-107044887-C-T

Variant names:

• chr4-107044887-C-T
• rs419178
• ENST00000513208.5:c.-78-118938G>A

Variant summary

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

The ENST00000513208.5(DKK2):​c.-78-118938G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,090 control chromosomes in the GnomAD database, including 41,307 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 0.74 (41307 hom., cov: 32)
• Consequence: DKK2 ENST00000513208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.775 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.-78-118938G>A		intron_variant	Intron 2 of 4	1		ENSP00000421255.1
DKK2	ENST00000510463.1	c.84+83055G>A		intron_variant	Intron 3 of 5	3		ENSP00000423797.1

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111781 AN: 151972 Hom.: 41272 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.736 AC: 111872 AN: 152090 Hom.: 41307 Cov.: 32 AF XY: 0.733 AC XY: 54517 AN XY: 74346

African (AFR) AF: 0.702 AC: 29121 AN: 41456

American (AMR) AF: 0.787 AC: 12030 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2521 AN: 3470

East Asian (EAS) AF: 0.795 AC: 4108 AN: 5170

South Asian (SAS) AF: 0.600 AC: 2894 AN: 4824

European-Finnish (FIN) AF: 0.774 AC: 8185 AN: 10574

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50606 AN: 67992

Other (OTH) AF: 0.750 AC: 1585 AN: 2112

Alfa AF: 0.740 Hom.: 6309

Bravo AF: 0.738

Asia WGS AF: 0.719 AC: 2501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.60
PhyloP100		-1.2
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: rs419178; hg19: chr4-107966044;