rs4956277

Positions:

• chr4-107025130-A-C
• chr4-107025130-A-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+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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DKK2	NM_014421.3	c.222+10240T>G		intron_variant		ENST00000285311.8	NP_055236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DKK2	ENST00000285311.8	c.222+10240T>G		intron_variant		1	NM_014421.3	ENSP00000285311	P1
DKK2	ENST00000513208.5	c.-78-99181T>G		intron_variant		1		ENSP00000421255
DKK2	ENST00000510534.1	n.443+10240T>G		intron_variant, non_coding_transcript_variant		1
DKK2	ENST00000510463.1	c.85-99181T>G		intron_variant		3		ENSP00000423797

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

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.224

Alfa AF: 0.171 Hom.: 631

Bravo AF: 0.250

Asia WGS AF: 0.391 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.51

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: rs4956277; hg19: chr4-107946287;