chr4-106932436-G-T

Position:

• chr4-106932436-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DKK2	NM_014421.3	c.223-6487C>A		intron_variant		ENST00000285311.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DKK2	ENST00000285311.8	c.223-6487C>A		intron_variant		1	NM_014421.3	P1
	ENST00000650850.1	n.932-2243G>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0609

Gnomad4 AMR AF: 0.0497

Gnomad4 ASJ AF: 0.0641

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0243

Gnomad4 FIN AF: 0.0571

Gnomad4 NFE AF: 0.0741

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0742 Hom.: 65

Bravo AF: 0.0582

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.13
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs10028834; hg19: chr4-107853593;