4-107194065-G-A

Variant names:

• chr4-107194065-G-A
• rs10516541
• ENST00000513208.5:c.-177-5540C>T

Variant summary

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

The ENST00000513208.5(DKK2):​c.-177-5540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,916 control chromosomes in the GnomAD database, including 9,006 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 0.32 (9006 hom., cov: 32)
• Consequence: DKK2 ENST00000513208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000513208.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK2	ENST00000513208.5	TSL:1	c.-177-5540C>T		intron	N/A	ENSP00000421255.1
	DKK2	ENST00000510463.1	TSL:3	c.-83-5540C>T		intron	N/A	ENSP00000423797.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48717 AN: 151798 Hom.: 9004 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.321 AC: 48727 AN: 151916 Hom.: 9006 Cov.: 32 AF XY: 0.319 AC XY: 23657 AN XY: 74274

African (AFR) AF: 0.139 AC: 5775 AN: 41472

American (AMR) AF: 0.364 AC: 5561 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1246 AN: 3462

East Asian (EAS) AF: 0.314 AC: 1613 AN: 5136

South Asian (SAS) AF: 0.203 AC: 979 AN: 4822

European-Finnish (FIN) AF: 0.414 AC: 4377 AN: 10562

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27963 AN: 67884

Other (OTH) AF: 0.328 AC: 692 AN: 2112

Alfa AF: 0.376 Hom.: 37451

Bravo AF: 0.311

Asia WGS AF: 0.247 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.63
DANN	Benign	0.45
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10516541; hg19: chr4-108115222;