rs6823507

Variant names:

• chr4-107040808-T-C
• rs6823507
• ENST00000513208.5:c.-78-114859A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000513208.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK2	ENST00000513208.5	TSL:1	c.-78-114859A>G		intron	N/A	ENSP00000421255.1	D6RGF1
	DKK2	ENST00000510463.1	TSL:3	c.84+87134A>G		intron	N/A	ENSP00000423797.1	D6RCC2

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

African (AFR) AF: 0.104 AC: 4300 AN: 41528

American (AMR) AF: 0.131 AC: 2007 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0799 AC: 277 AN: 3468

East Asian (EAS) AF: 0.225 AC: 1164 AN: 5176

South Asian (SAS) AF: 0.130 AC: 629 AN: 4828

European-Finnish (FIN) AF: 0.192 AC: 2032 AN: 10562

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0855 AC: 5815 AN: 67980

Other (OTH) AF: 0.108 AC: 228 AN: 2114

Alfa AF: 0.0896 Hom.: 333

Bravo AF: 0.103

Asia WGS AF: 0.215 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.84
PhyloP100		-0.42
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: rs6823507; hg19: chr4-107961965;