11-12003029-G-T

Variant names:

• chr11-12003029-G-T
• rs12575803
• NM_001018057.2:c.214-592C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018057.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK3	NM_001018057.2	MANE Select	c.214-592C>A		intron	N/A	NP_001018067.1
	DKK3	NM_001330220.3		c.214-592C>A		intron	N/A	NP_001317149.1
	DKK3	NM_013253.5		c.214-592C>A		intron	N/A	NP_037385.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK3	ENST00000683431.1	MANE Select	c.214-592C>A		intron	N/A	ENSP00000506835.1
	DKK3	ENST00000326932.8	TSL:1	c.214-592C>A		intron	N/A	ENSP00000314910.4
	DKK3	ENST00000396505.7	TSL:1	c.214-592C>A		intron	N/A	ENSP00000379762.2

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

African (AFR) AF: 0.0227 AC: 944 AN: 41562

American (AMR) AF: 0.0807 AC: 1235 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3472

East Asian (EAS) AF: 0.105 AC: 544 AN: 5188

South Asian (SAS) AF: 0.179 AC: 861 AN: 4822

European-Finnish (FIN) AF: 0.0877 AC: 931 AN: 10620

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8201 AN: 68012

Other (OTH) AF: 0.0965 AC: 204 AN: 2114

Alfa AF: 0.106 Hom.: 481

Bravo AF: 0.0829

Asia WGS AF: 0.131 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.52
PhyloP100		0.077
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: rs12575803; hg19: chr11-12024576;