rs17037297

Positions:

• chr4-107034566-G-C
• chr4-107034566-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DKK2	NM_014421.3	c.222+804C>G		intron_variant		ENST00000285311.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DKK2	ENST00000285311.8	c.222+804C>G		intron_variant		1	NM_014421.3	P1
DKK2	ENST00000513208.5	c.-78-108617C>G		intron_variant		1
DKK2	ENST00000510534.1	n.443+804C>G		intron_variant, non_coding_transcript_variant		1
DKK2	ENST00000510463.1	c.84+93376C>G		intron_variant		3

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

Gnomad4 AFR AF: 0.0223

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0357

Gnomad4 OTH AF: 0.0638

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs17037297; hg19: chr4-107955723;