rs2308292

chr4-106968614-TTTAAG-Tchr4-106968614-TTTAAG-TTTAAGTTAAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_014421.3(DKK2):c.223-42670_223-42666del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,776 control chromosomes in the GnomAD database, including 10,872 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (10872 hom., cov: 0)
• Consequence: DKK2 NM_014421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DKK2	NM_014421.3	c.223-42670_223-42666del		intron_variant		ENST00000285311.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DKK2	ENST00000285311.8	c.223-42670_223-42666del		intron_variant		1	NM_014421.3	P1
DKK2	ENST00000513208.5	c.-78-42670_-78-42666del		intron_variant		1
DKK2	ENST00000510534.1	n.444-42670_444-42666del		intron_variant, non_coding_transcript_variant		1
DKK2	ENST00000510463.1	c.85-42670_85-42666del		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57364 AN: 151658 Hom.: 10865 Cov.: 0

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.378 AC: 57412 AN: 151776 Hom.: 10872 Cov.: 0 AF XY: 0.378 AC XY: 28031 AN XY: 74162

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.381

Alfa AF: 0.368 Hom.: 1272

Bravo AF: 0.378

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2308292; hg19: chr4-107889771;