11-12003029-G-T

Variant summary

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

The NM_001018057.2(DKK3):c.214-592C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 152,292 control chromosomes in the GnomAD database, including 760 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 0.088 (760 hom., cov: 32)
• Consequence: DKK3 NM_001018057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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 (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DKK3	NM_001018057.2	c.214-592C>A		intron_variant		ENST00000683431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DKK3	ENST00000683431.1	c.214-592C>A		intron_variant			NM_001018057.2	P1

Frequencies

GnomAD3 genomes AF: 0.0885 AC: 13465 AN: 152172 Hom.: 761 Cov.: 32

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0877

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.0884 AC: 13463 AN: 152292 Hom.: 760 Cov.: 32 AF XY: 0.0881 AC XY: 6561 AN XY: 74472

Gnomad4 AFR AF: 0.0227

Gnomad4 AMR AF: 0.0807

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.0877

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0965

Alfa AF: 0.104 Hom.: 418

Bravo AF: 0.0829

Asia WGS AF: 0.131 AC: 453 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	0.19
Dann	Benign	0.52

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: rs12575803; hg19: chr11-12024576;