rs10028834

Variant names:

• chr4-106932436-G-T
• rs10028834
• NM_014421.3:c.223-6487C>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.223-6487C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 152,156 control chromosomes in the GnomAD database, including 316 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 0.062 (316 hom., cov: 32)
• Consequence: DKK2 NM_014421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0724 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.223-6487C>A		intron	N/A	NP_055236.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK2	ENST00000285311.8	TSL:1 MANE Select	c.223-6487C>A		intron	N/A	ENSP00000285311.3
	DKK2	ENST00000513208.5	TSL:1	c.-78-6487C>A		intron	N/A	ENSP00000421255.1
	DKK2	ENST00000510534.1	TSL:1	n.444-6487C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9386 AN: 152038 Hom.: 314 Cov.: 32

Gnomad AFR AF: 0.0606

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0497

Gnomad ASJ AF: 0.0641

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.0584

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

GnomAD4 genome AF: 0.0618 AC: 9402 AN: 152156 Hom.: 316 Cov.: 32 AF XY: 0.0595 AC XY: 4427 AN XY: 74390

African (AFR) AF: 0.0609 AC: 2528 AN: 41538

American (AMR) AF: 0.0497 AC: 759 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0641 AC: 222 AN: 3466

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0243 AC: 117 AN: 4820

European-Finnish (FIN) AF: 0.0571 AC: 605 AN: 10598

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0741 AC: 5038 AN: 67960

Other (OTH) AF: 0.0578 AC: 122 AN: 2112

Alfa AF: 0.0741 Hom.: 71

Bravo AF: 0.0582

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.13
DANN	Benign	0.34
PhyloP100		-0.50
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: rs10028834; hg19: chr4-107853593;