NM_014421.3:c.222+804C>G

Variant names:

• chr4-107034566-G-C
• rs17037297
• NM_014421.3:c.222+804C>G

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+804C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 152,244 control chromosomes in the GnomAD database, including 464 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 0.057 (464 hom., cov: 32)
• Consequence: DKK2 NM_014421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 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+804C>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+804C>G		intron	N/A	ENSP00000285311.3
	DKK2	ENST00000513208.5	TSL:1	c.-78-108617C>G		intron	N/A	ENSP00000421255.1
	DKK2	ENST00000510534.1	TSL:1	n.443+804C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0568 AC: 8634 AN: 152126 Hom.: 465 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0640

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

GnomAD4 genome AF: 0.0567 AC: 8636 AN: 152244 Hom.: 464 Cov.: 32 AF XY: 0.0635 AC XY: 4726 AN XY: 74428

African (AFR) AF: 0.0223 AC: 926 AN: 41564

American (AMR) AF: 0.116 AC: 1776 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3470

East Asian (EAS) AF: 0.235 AC: 1215 AN: 5162

South Asian (SAS) AF: 0.145 AC: 701 AN: 4818

European-Finnish (FIN) AF: 0.115 AC: 1224 AN: 10600

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0357 AC: 2428 AN: 68022

Other (OTH) AF: 0.0638 AC: 135 AN: 2116

Alfa AF: 0.0181 Hom.: 9

Bravo AF: 0.0533

Asia WGS AF: 0.209 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.38
PhyloP100		-0.20
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: rs17037297; hg19: chr4-107955723;