rs7690634

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-106995352-T-A
• chr4-106995352-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK2	NM_014421.3	c.222+40018A>T		intron_variant	Intron 1 of 3	ENST00000285311.8	NP_055236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DKK2	ENST00000285311.8	c.222+40018A>T		intron_variant	Intron 1 of 3	1	NM_014421.3	ENSP00000285311.3
DKK2	ENST00000513208.5	c.-78-69403A>T		intron_variant	Intron 2 of 4	1		ENSP00000421255.1
DKK2	ENST00000510534.1	n.443+40018A>T		intron_variant	Intron 1 of 2	1
DKK2	ENST00000510463.1	c.85-69403A>T		intron_variant	Intron 3 of 5	3		ENSP00000423797.1

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

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.154

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 v4.3

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