rs10516540

Variant names:

• chr4-107187148-T-G
• rs10516540
• ENST00000513208.5:c.-79+1279A>C

Variant summary

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

The ENST00000513208.5(DKK2):​c.-79+1279A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 151,878 control chromosomes in the GnomAD database, including 354 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 0.042 (354 hom., cov: 32)
• Consequence: DKK2 ENST00000513208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DKK2	ENST00000513208.5	c.-79+1279A>C		intron_variant	Intron 2 of 4	1		ENSP00000421255.1
DKK2	ENST00000510463.1	c.16+1279A>C		intron_variant	Intron 2 of 5	3		ENSP00000423797.1

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6429 AN: 151760 Hom.: 352 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.0217

Gnomad EAS AF: 0.0796

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00466

Gnomad OTH AF: 0.0466

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

GnomAD4 genome AF: 0.0424 AC: 6435 AN: 151878 Hom.: 354 Cov.: 32 AF XY: 0.0427 AC XY: 3167 AN XY: 74228

African (AFR) AF: 0.120 AC: 4979 AN: 41472

American (AMR) AF: 0.0214 AC: 326 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.0217 AC: 75 AN: 3458

East Asian (EAS) AF: 0.0798 AC: 410 AN: 5136

South Asian (SAS) AF: 0.0439 AC: 212 AN: 4826

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10618

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00466 AC: 316 AN: 67822

Other (OTH) AF: 0.0471 AC: 99 AN: 2104

Alfa AF: 0.0319 Hom.: 30

Bravo AF: 0.0478

Asia WGS AF: 0.0670 AC: 231 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.9
DANN	Benign	0.70
PhyloP100		0.25
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: rs10516540; hg19: chr4-108108305;