rs6823507

Positions:

• chr4-107040808-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000513208.5(DKK2):​c.-78-114859A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,148 control chromosomes in the GnomAD database, including 1,036 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 0.11 (1036 hom., cov: 33)
• Consequence: DKK2 ENST00000513208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DKK2	ENST00000513208.5	c.-78-114859A>G		intron_variant		1
DKK2	ENST00000510463.1	c.84+87134A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16462 AN: 152030 Hom.: 1032 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0799

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0855

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.108 AC: 16488 AN: 152148 Hom.: 1036 Cov.: 33 AF XY: 0.114 AC XY: 8478 AN XY: 74378

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0799

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.0855

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0902 Hom.: 296

Bravo AF: 0.103

Asia WGS AF: 0.215 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6823507; hg19: chr4-107961965;