4-106922336-G-A

Variant names:

• chr4-106922336-G-A
• rs10488898
• NM_014421.3:c.*1618C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014421.3(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 NM_014421.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 7 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:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK2	NM_014421.3	MANE Select	c.*1618C>T		3_prime_UTR	Exon 4 of 4	NP_055236.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK2	ENST00000285311.8	TSL:1 MANE Select	c.*1618C>T		3_prime_UTR	Exon 4 of 4	ENSP00000285311.3
	ENSG00000286147	ENST00000650850.1		n.931+2148G>A		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

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) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.145 AC: 6038 AN: 41520

American (AMR) AF: 0.0621 AC: 949 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 233 AN: 3470

East Asian (EAS) AF: 0.0563 AC: 292 AN: 5184

South Asian (SAS) AF: 0.119 AC: 573 AN: 4824

European-Finnish (FIN) AF: 0.0679 AC: 719 AN: 10590

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0665 AC: 4520 AN: 67984

Other (OTH) AF: 0.0966 AC: 204 AN: 2112

Alfa AF: 0.0735 Hom.: 2003

Bravo AF: 0.0901

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.66
DANN	Benign	0.61
PhyloP100		-0.037
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: rs10488898; hg19: chr4-107843493;