rs6827902

Variant names:

• chr4-107032857-C-A
• rs6827902
• NM_014421.3:c.222+2513G>T

Variant summary

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

The NM_014421.3(DKK2):​c.222+2513G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 151,990 control chromosomes in the GnomAD database, including 39,253 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 0.71 (39253 hom., cov: 33)
• Consequence: DKK2 NM_014421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014421.3. 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
	DKK2	NM_014421.3	MANE Select	c.222+2513G>T		intron	N/A	NP_055236.1	Q9UBU2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK2	ENST00000285311.8	TSL:1 MANE Select	c.222+2513G>T		intron	N/A	ENSP00000285311.3	Q9UBU2
	DKK2	ENST00000513208.5	TSL:1	c.-78-106908G>T		intron	N/A	ENSP00000421255.1	D6RGF1
	DKK2	ENST00000510534.1	TSL:1	n.443+2513G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108460 AN: 151874 Hom.: 39228 Cov.: 33

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.714 AC: 108530 AN: 151990 Hom.: 39253 Cov.: 33 AF XY: 0.711 AC XY: 52778 AN XY: 74272

African (AFR) AF: 0.679 AC: 28157 AN: 41476

American (AMR) AF: 0.631 AC: 9636 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2557 AN: 3468

East Asian (EAS) AF: 0.457 AC: 2360 AN: 5168

South Asian (SAS) AF: 0.656 AC: 3158 AN: 4814

European-Finnish (FIN) AF: 0.747 AC: 7877 AN: 10550

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52377 AN: 67916

Other (OTH) AF: 0.700 AC: 1479 AN: 2112

Alfa AF: 0.750 Hom.: 32505

Bravo AF: 0.701

Asia WGS AF: 0.595 AC: 2067 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6827902; hg19: chr4-107954014;