chr4-106995352-T-A

Variant names:

• chr4-106995352-T-A
• rs7690634
• NM_014421.3:c.222+40018A>T

Variant summary

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

The NM_014421.3(DKK2):​c.222+40018A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,126 control chromosomes in the GnomAD database, including 1,762 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 0.15 (1762 hom., cov: 32)
• Consequence: DKK2 NM_014421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014421.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK2	NM_014421.3	MANE Select	c.222+40018A>T		intron	N/A	NP_055236.1	Q9UBU2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK2	ENST00000285311.8	TSL:1 MANE Select	c.222+40018A>T		intron	N/A	ENSP00000285311.3	Q9UBU2
	DKK2	ENST00000513208.5	TSL:1	c.-78-69403A>T		intron	N/A	ENSP00000421255.1	D6RGF1
	DKK2	ENST00000510534.1	TSL:1	n.443+40018A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22752 AN: 152008 Hom.: 1756 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.150 AC: 22798 AN: 152126 Hom.: 1762 Cov.: 32 AF XY: 0.152 AC XY: 11304 AN XY: 74362

African (AFR) AF: 0.169 AC: 7002 AN: 41508

American (AMR) AF: 0.217 AC: 3311 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1118 AN: 5158

South Asian (SAS) AF: 0.176 AC: 850 AN: 4822

European-Finnish (FIN) AF: 0.130 AC: 1376 AN: 10588

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8195 AN: 67994

Other (OTH) AF: 0.154 AC: 324 AN: 2110

Alfa AF: 0.0547 Hom.: 50

Bravo AF: 0.158

Asia WGS AF: 0.208 AC: 721 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.0
DANN	Benign	0.52
PhyloP100		0.11
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: rs7690634; hg19: chr4-107916509;