rs419558

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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:58864):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014421.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK2	NM_014421.3	MANE Select	c.*1019G>A		3_prime_UTR	Exon 4 of 4	NP_055236.1	Q9UBU2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK2	ENST00000285311.8	TSL:1 MANE Select	c.*1019G>A		3_prime_UTR	Exon 4 of 4	ENSP00000285311.3	Q9UBU2
	DKK2	ENST00000949483.1		c.*1019G>A		3_prime_UTR	Exon 3 of 3	ENSP00000619542.1
	ENSG00000286147	ENST00000650850.1		n.931+2747C>T		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.357 AC: 14806 AN: 41470

American (AMR) AF: 0.197 AC: 3012 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 941 AN: 3466

East Asian (EAS) AF: 0.272 AC: 1402 AN: 5156

South Asian (SAS) AF: 0.205 AC: 989 AN: 4820

European-Finnish (FIN) AF: 0.323 AC: 3416 AN: 10574

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.263 AC: 17841 AN: 67956

Other (OTH) AF: 0.266 AC: 563 AN: 2116

Alfa AF: 0.265 Hom.: 20576

Bravo AF: 0.276

Asia WGS AF: 0.227 AC: 788 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.70
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs419558; hg19: chr4-107844092;