Genetic Variant DKK2:c.*954G>A (chr4-106923000-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014421.3(DKK2):c.*954G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,012 control chromosomes in the GnomAD database, including 9,690 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 ( 9690 hom., cov: 33)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

DKK2
NM_014421.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.835

Variant links:

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]

DKK2 links:

ENSG00000286147 (HGNC:):

ENSG00000286147 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK2	NM_014421.3 link	c.*954G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000285311.8	NP_055236.1	Q9UBU2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DKK2	ENST00000285311 link	c.*954G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_014421.3	ENSP00000285311.3		Q9UBU2
ENSG00000286147	ENST00000650850.1 link	n.931+2812C>T		intron_variant	Intron 10 of 10

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53317

AN:

151892

Hom.:

9665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.323

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

Gnomad4 NFE exome

AF:

0.500

GnomAD4 genome

AF:

0.351

AC:

53391

AN:

152010

Hom.:

9690

Cov.:

AF XY:

0.348

AC XY:

25844

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.434

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.336

Gnomad4 EAS

AF:

0.273

Gnomad4 SAS

AF:

0.230

Gnomad4 FIN

AF:

0.380

Gnomad4 NFE

AF:

0.337

Gnomad4 OTH

AF:

0.329

Alfa

AF:

0.321

Hom.:

10283

Bravo

AF:

0.339

Asia WGS

AF:

0.252

AC:

875

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

0.31

DANN

Benign

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over