11-11999069-C-T

Position:

• chr11-11999069-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001018057.2(DKK3):​c.352-290G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,034 control chromosomes in the GnomAD database, including 4,177 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 0.22 (4177 hom., cov: 32)
• Consequence: DKK3 NM_001018057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847

Genes affected

DKK3 (HGNC:2893): (dickkopf WNT signaling pathway inhibitor 3) 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. The expression of this gene is decreased in a variety of cancer cell lines and it may function as a tumor suppressor gene. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DKK3	NM_001018057.2	c.352-290G>A		intron_variant		ENST00000683431.1	NP_001018067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DKK3	ENST00000683431.1	c.352-290G>A		intron_variant			NM_001018057.2	ENSP00000506835	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33606 AN: 151916 Hom.: 4164 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0857

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.221 AC: 33650 AN: 152034 Hom.: 4177 Cov.: 32 AF XY: 0.221 AC XY: 16408 AN XY: 74336

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.0861

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.210

Alfa AF: 0.186 Hom.: 2639

Bravo AF: 0.237

Asia WGS AF: 0.174 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.63

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: rs7104941; hg19: chr11-12020616;