rs17509845

chr4-106969864-G-Achr4-106969864-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014421.3(DKK2):c.223-43915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 152,084 control chromosomes in the GnomAD database, including 77 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 0.027 (77 hom., cov: 32)
• Consequence: DKK2 NM_014421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0269 (4090/152084) while in subpopulation NFE AF= 0.0408 (2773/67988). AF 95% confidence interval is 0.0395. There are 77 homozygotes in gnomad4. There are 1965 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 4090 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DKK2	NM_014421.3	c.223-43915C>T		intron_variant		ENST00000285311.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DKK2	ENST00000285311.8	c.223-43915C>T		intron_variant		1	NM_014421.3	P1
DKK2	ENST00000513208.5	c.-78-43915C>T		intron_variant		1
DKK2	ENST00000510534.1	n.444-43915C>T		intron_variant, non_coding_transcript_variant		1
DKK2	ENST00000510463.1	c.85-43915C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4090 AN: 151966 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.00778

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0408

Gnomad OTH AF: 0.0283

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

GnomAD4 genome AF: 0.0269 AC: 4090 AN: 152084 Hom.: 77 Cov.: 32 AF XY: 0.0264 AC XY: 1965 AN XY: 74338

Gnomad4 AFR AF: 0.00776

Gnomad4 AMR AF: 0.0255

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00499

Gnomad4 FIN AF: 0.0398

Gnomad4 NFE AF: 0.0408

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0196 Hom.: 7

Bravo AF: 0.0264

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.78
Dann	Benign	0.61

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: rs17509845; hg19: chr4-107891021;