4-106922336-G-A

Position:

• chr4-106922336-G-A

Variant summary

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

The ENST00000285311.8(DKK2):​c.*1618C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0893 in 152,178 control chromosomes in the GnomAD database, including 726 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 0.089 (726 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: DKK2 ENST00000285311.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DKK2	NM_014421.3	c.*1618C>T		3_prime_UTR_variant	4/4	ENST00000285311.8	NP_055236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DKK2	ENST00000285311.8	c.*1618C>T		3_prime_UTR_variant	4/4	1	NM_014421.3	ENSP00000285311	P1
	ENST00000650850.1	n.931+2148G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13568 AN: 152060 Hom.: 724 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0622

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.0564

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0665

Gnomad OTH AF: 0.0962

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0893 AC: 13582 AN: 152178 Hom.: 726 Cov.: 33 AF XY: 0.0900 AC XY: 6698 AN XY: 74382

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0621

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.0563

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0679

Gnomad4 NFE AF: 0.0665

Gnomad4 OTH AF: 0.0966

Alfa AF: 0.0718 Hom.: 886

Bravo AF: 0.0901

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.66
DANN	Benign	0.61

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: rs10488898; hg19: chr4-107843493;