rs10516541

chr4-107194065-G-Achr4-107194065-G-C

Variant summary

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

The ENST00000513208.5(DKK2):c.-177-5540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,916 control chromosomes in the GnomAD database, including 9,006 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 0.32 (9006 hom., cov: 32)
• Consequence: DKK2 ENST00000513208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 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.-177-5540C>T		intron_variant		1
DKK2	ENST00000510463.1	c.-83-5540C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48717 AN: 151798 Hom.: 9004 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.321 AC: 48727 AN: 151916 Hom.: 9006 Cov.: 32 AF XY: 0.319 AC XY: 23657 AN XY: 74274

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.328

Alfa AF: 0.383 Hom.: 15311

Bravo AF: 0.311

Asia WGS AF: 0.247 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.63
Dann	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10516541; hg19: chr4-108115222;