rs17510191

Positions:

• chr4-107059548-T-C

Variant summary

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

The ENST00000513208.5(DKK2):​c.-79+128879A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,060 control chromosomes in the GnomAD database, including 1,516 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 0.13 (1516 hom., cov: 32)
• Consequence: DKK2 ENST00000513208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 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.-79+128879A>G		intron_variant		1
DKK2	ENST00000510463.1	c.84+68394A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19368 AN: 151942 Hom.: 1516 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.0972

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.127 AC: 19359 AN: 152060 Hom.: 1516 Cov.: 32 AF XY: 0.125 AC XY: 9320 AN XY: 74342

Gnomad4 AFR AF: 0.0480

Gnomad4 AMR AF: 0.0971

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0267

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.122

Alfa AF: 0.158 Hom.: 628

Bravo AF: 0.115

Asia WGS AF: 0.0790 AC: 273 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17510191; hg19: chr4-107980705;