NM_014421.3:c.223-42670_223-42666delCTTAA

Variant names:

• chr4-106968614-TTTAAG-T
• rs2308292
• NM_014421.3:c.223-42670_223-42666delCTTAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014421.3(DKK2):​c.223-42670_223-42666delCTTAA variant causes a intron change involving the alteration of a non-conserved nucleotide. 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
• Publications: 6 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 -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 rank	MANE	Protein	UniProt
DKK2	NM_014421.3	c.223-42670_223-42666delCTTAA		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.223-42670_223-42666delCTTAA		intron_variant	Intron 1 of 3	1	NM_014421.3	ENSP00000285311.3
DKK2	ENST00000513208.5	c.-78-42670_-78-42666delCTTAA		intron_variant	Intron 2 of 4	1		ENSP00000421255.1
DKK2	ENST00000510534.1	n.444-42670_444-42666delCTTAA		intron_variant	Intron 1 of 2	1
DKK2	ENST00000510463.1	c.85-42670_85-42666delCTTAA		intron_variant	Intron 3 of 5	3		ENSP00000423797.1

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

African (AFR) AF: 0.444 AC: 18369 AN: 41394

American (AMR) AF: 0.340 AC: 5177 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1212 AN: 3468

East Asian (EAS) AF: 0.465 AC: 2390 AN: 5142

South Asian (SAS) AF: 0.261 AC: 1256 AN: 4812

European-Finnish (FIN) AF: 0.387 AC: 4086 AN: 10552

Middle Eastern (MID) AF: 0.297 AC: 86 AN: 290

European-Non Finnish (NFE) AF: 0.348 AC: 23641 AN: 67884

Other (OTH) AF: 0.381 AC: 803 AN: 2108

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
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: rs2308292; hg19: chr4-107889771;