rs2073664

Positions:

• chr8-42374268-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014420.3(DKK4):​c.507C>T​(p.Val169=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,613,456 control chromosomes in the GnomAD database, including 21,910 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 0.24 (8417 hom., cov: 32)
  • Exomes 𝑓: 0.098 (13493 hom.)
• Consequence: DKK4 NM_014420.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316

Genes affected

DKK4 (HGNC:2894): (dickkopf WNT signaling pathway inhibitor 4) 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. Activity of this protein is modulated by binding to the Wnt co-receptor and the co-factor kremen 2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.316 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DKK4	NM_014420.3	c.507C>T	p.Val169=	synonymous_variant	4/4	ENST00000220812.3
DKK4	XM_011544488.3	c.507C>T	p.Val169=	synonymous_variant	5/5
DKK4	XM_017013316.2	c.507C>T	p.Val169=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DKK4	ENST00000220812.3	c.507C>T	p.Val169=	synonymous_variant	4/4	1	NM_014420.3	P1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36098 AN: 151788 Hom.: 8383 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0714

Gnomad OTH AF: 0.194

GnomAD3 exomes AF: 0.137 AC: 34467 AN: 251080 Hom.: 4866 AF XY: 0.132 AC XY: 17902 AN XY: 135714

Gnomad AFR exome AF: 0.617

Gnomad AMR exome AF: 0.0685

Gnomad ASJ exome AF: 0.0650

Gnomad EAS exome AF: 0.125

Gnomad SAS exome AF: 0.218

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.0718

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.0981 AC: 143410 AN: 1461550 Hom.: 13493 Cov.: 32 AF XY: 0.0997 AC XY: 72463 AN XY: 727082

Gnomad4 AFR exome AF: 0.627

Gnomad4 AMR exome AF: 0.0739

Gnomad4 ASJ exome AF: 0.0668

Gnomad4 EAS exome AF: 0.149

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.0689

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.238 AC: 36175 AN: 151906 Hom.: 8417 Cov.: 32 AF XY: 0.240 AC XY: 17829 AN XY: 74252

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0642

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.0714

Gnomad4 OTH AF: 0.195

Alfa AF: 0.139 Hom.: 2261

Bravo AF: 0.246

Asia WGS AF: 0.273 AC: 952 AN: 3478

EpiCase AF: 0.0650

EpiControl AF: 0.0679

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.6
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2073664; hg19: chr8-42231786; COSMIC: COSV55184528; COSMIC: COSV55184528;