rs4956277

Variant names:

• chr4-107025130-A-C
• rs4956277
• NM_014421.3:c.222+10240T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-107025130-A-C
• chr4-107025130-A-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+10240T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,974 control chromosomes in the GnomAD database, including 4,636 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 0.24 (4636 hom., cov: 32)
• Consequence: DKK2 NM_014421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.509 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK2	NM_014421.3	MANE Select	c.222+10240T>G		intron	N/A	NP_055236.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK2	ENST00000285311.8	TSL:1 MANE Select	c.222+10240T>G		intron	N/A	ENSP00000285311.3
	DKK2	ENST00000513208.5	TSL:1	c.-78-99181T>G		intron	N/A	ENSP00000421255.1
	DKK2	ENST00000510534.1	TSL:1	n.443+10240T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35920 AN: 151856 Hom.: 4618 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.237 AC: 35980 AN: 151974 Hom.: 4636 Cov.: 32 AF XY: 0.238 AC XY: 17710 AN XY: 74280

African (AFR) AF: 0.213 AC: 8839 AN: 41444

American (AMR) AF: 0.326 AC: 4977 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 732 AN: 3462

East Asian (EAS) AF: 0.526 AC: 2675 AN: 5090

South Asian (SAS) AF: 0.277 AC: 1334 AN: 4824

European-Finnish (FIN) AF: 0.194 AC: 2060 AN: 10594

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14579 AN: 67972

Other (OTH) AF: 0.224 AC: 473 AN: 2110

Alfa AF: 0.171 Hom.: 643

Bravo AF: 0.250

Asia WGS AF: 0.391 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.51
PhyloP100		-0.043
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: rs4956277; hg19: chr4-107946287;