rs447372

Variant names:

• chr4-106932839-G-A
• rs447372
• NM_014421.3:c.223-6890C>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.223-6890C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,964 control chromosomes in the GnomAD database, including 18,369 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 0.47 (18369 hom., cov: 32)
• Consequence: DKK2 NM_014421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK2	NM_014421.3	c.223-6890C>T		intron_variant	Intron 1 of 3	ENST00000285311.8	NP_055236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DKK2	ENST00000285311.8	c.223-6890C>T		intron_variant	Intron 1 of 3	1	NM_014421.3	ENSP00000285311.3

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71280 AN: 151846 Hom.: 18328 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.470 AC: 71377 AN: 151964 Hom.: 18369 Cov.: 32 AF XY: 0.467 AC XY: 34676 AN XY: 74268

African (AFR) AF: 0.685 AC: 28374 AN: 41442

American (AMR) AF: 0.322 AC: 4916 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1395 AN: 3468

East Asian (EAS) AF: 0.330 AC: 1704 AN: 5156

South Asian (SAS) AF: 0.348 AC: 1675 AN: 4820

European-Finnish (FIN) AF: 0.449 AC: 4733 AN: 10536

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.401 AC: 27271 AN: 67950

Other (OTH) AF: 0.446 AC: 940 AN: 2108

Alfa AF: 0.474 Hom.: 2784

Bravo AF: 0.464

Asia WGS AF: 0.346 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.71
DANN	Benign	0.29
PhyloP100		-0.78
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: rs447372; hg19: chr4-107853996;