rs10488899

Variant names:

• chr4-106943654-T-G
• rs10488899
• NM_014421.3:c.223-17705A>C

Variant summary

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

The NM_014421.3(DKK2):​c.223-17705A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,106 control chromosomes in the GnomAD database, including 1,867 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 0.13 (1867 hom., cov: 32)
• Consequence: DKK2 NM_014421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK2	NM_014421.3	c.223-17705A>C		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.223-17705A>C		intron_variant	Intron 1 of 3	1	NM_014421.3	ENSP00000285311.3
DKK2	ENST00000513208.5	c.-78-17705A>C		intron_variant	Intron 2 of 4	1		ENSP00000421255.1
DKK2	ENST00000510534.1	n.444-17705A>C		intron_variant	Intron 1 of 2	1
DKK2	ENST00000510463.1	c.85-17705A>C		intron_variant	Intron 3 of 5	3		ENSP00000423797.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20316 AN: 151988 Hom.: 1866 Cov.: 32

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.134 AC: 20312 AN: 152106 Hom.: 1867 Cov.: 32 AF XY: 0.131 AC XY: 9716 AN XY: 74362

African (AFR) AF: 0.0324 AC: 1348 AN: 41550

American (AMR) AF: 0.117 AC: 1777 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 670 AN: 3466

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.123 AC: 595 AN: 4830

European-Finnish (FIN) AF: 0.162 AC: 1718 AN: 10592

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13627 AN: 67940

Other (OTH) AF: 0.145 AC: 305 AN: 2106

Alfa AF: 0.182 Hom.: 8212

Bravo AF: 0.127

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.27
DANN	Benign	0.73
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10488899; hg19: chr4-107864811;