rs419558

Variant names:

• chr4-106922935-C-T
• rs419558
• NM_014421.3:c.*1019G>A

Variant summary

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

The NM_014421.3(DKK2):​c.*1019G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,024 control chromosomes in the GnomAD database, including 6,386 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 0.28 (6386 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DKK2 NM_014421.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141

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]

ENSG00000286147 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK2	NM_014421.3	c.*1019G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000285311.8	NP_055236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DKK2	ENST00000285311	c.*1019G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_014421.3	ENSP00000285311.3
ENSG00000286147	ENST00000650850.1	n.931+2747C>T		intron_variant	Intron 10 of 10

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43226 AN: 151906 Hom.: 6376 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.260

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.285 AC: 43270 AN: 152024 Hom.: 6386 Cov.: 32 AF XY: 0.284 AC XY: 21073 AN XY: 74314

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.266

Alfa AF: 0.263 Hom.: 8738

Bravo AF: 0.276

Asia WGS AF: 0.227 AC: 788 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.70

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: rs419558; hg19: chr4-107844092;