4-107044887-C-T

Position:

• chr4-107044887-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
		n.107044887C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DKK2	ENST00000513208.5	c.-78-118938G>A		intron_variant		1		ENSP00000421255.1
DKK2	ENST00000510463.1	c.84+83055G>A		intron_variant		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

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.750

Alfa AF: 0.741 Hom.: 6102

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs419178; hg19: chr4-107966044;