NM_014421.3:c.222+5167C>T

Variant names:

• chr4-107030203-G-A
• rs10021344
• NM_014421.3:c.222+5167C>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.222+5167C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,786 control chromosomes in the GnomAD database, including 11,949 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 0.37 (11949 hom., cov: 33)
• Consequence: DKK2 NM_014421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK2	NM_014421.3	c.222+5167C>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.222+5167C>T		intron_variant	Intron 1 of 3	1	NM_014421.3	ENSP00000285311.3
DKK2	ENST00000513208.5	c.-78-104254C>T		intron_variant	Intron 2 of 4	1		ENSP00000421255.1
DKK2	ENST00000510534.1	n.443+5167C>T		intron_variant	Intron 1 of 2	1
DKK2	ENST00000510463.1	c.84+97739C>T		intron_variant	Intron 3 of 5	3		ENSP00000423797.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56662 AN: 151668 Hom.: 11952 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.0201

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.373 AC: 56662 AN: 151786 Hom.: 11949 Cov.: 33 AF XY: 0.364 AC XY: 26970 AN XY: 74178

African (AFR) AF: 0.246 AC: 10187 AN: 41438

American (AMR) AF: 0.299 AC: 4567 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1492 AN: 3462

East Asian (EAS) AF: 0.0201 AC: 104 AN: 5172

South Asian (SAS) AF: 0.192 AC: 927 AN: 4820

European-Finnish (FIN) AF: 0.427 AC: 4499 AN: 10536

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33585 AN: 67792

Other (OTH) AF: 0.373 AC: 787 AN: 2110

Alfa AF: 0.450 Hom.: 29953

Bravo AF: 0.358

Asia WGS AF: 0.122 AC: 427 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.60
PhyloP100		0.53
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: rs10021344; hg19: chr4-107951360;