4-107227251-C-T

Position:

• chr4-107227251-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000513208.5(DKK2):​c.-177-38726G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,110 control chromosomes in the GnomAD database, including 12,907 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 0.37 (12907 hom., cov: 32)
• Consequence: DKK2 ENST00000513208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DKK2	ENST00000513208.5	c.-177-38726G>A		intron_variant		1
DKK2	ENST00000510463.1	c.-83-38726G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56272 AN: 151992 Hom.: 12904 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.370 AC: 56262 AN: 152110 Hom.: 12907 Cov.: 32 AF XY: 0.378 AC XY: 28125 AN XY: 74350

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.389

Alfa AF: 0.445 Hom.: 35739

Bravo AF: 0.370

Asia WGS AF: 0.554 AC: 1927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.4
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs959482; hg19: chr4-108148408;