rs11022095

Positions:

• chr11-11965380-A-G

Variant summary

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

The NM_001018057.2(DKK3):​c.830+429T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,098 control chromosomes in the GnomAD database, including 9,832 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 0.35 (9832 hom., cov: 33)
• Consequence: DKK3 NM_001018057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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 (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DKK3	NM_001018057.2	c.830+429T>C		intron_variant		ENST00000683431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DKK3	ENST00000683431.1	c.830+429T>C		intron_variant			NM_001018057.2	P1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53786 AN: 151980 Hom.: 9826 Cov.: 33

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.354 AC: 53817 AN: 152098 Hom.: 9832 Cov.: 33 AF XY: 0.353 AC XY: 26232 AN XY: 74356

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.372

Alfa AF: 0.377 Hom.: 2273

Bravo AF: 0.349

Asia WGS AF: 0.396 AC: 1380 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	0.031
DANN	Benign	0.47

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: rs11022095; hg19: chr11-11986927;