dbSNP rs3733635: DKK2:c.-157T>C (chr4-107035748-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014421.3(DKK2):c.-157T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 687,612 control chromosomes in the GnomAD database, including 4,114 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 0.093 ( 866 hom., cov: 32)

Exomes 𝑓: 0.10 ( 3248 hom. )

Consequence

DKK2
NM_014421.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK2	NM_014421.3 link	c.-157T>C		5_prime_UTR_variant	Exon 1 of 4	ENST00000285311.8	NP_055236.1	Q9UBU2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DKK2	ENST00000285311.8 link	c.-157T>C	5_prime_UTR_variant	Exon 1 of 4	1	NM_014421.3	ENSP00000285311.3	Q9UBU2
DKK2	ENST00000513208.5 link	c.-78-109799T>C	intron_variant	Intron 2 of 4	1		ENSP00000421255.1	D6RGF1
DKK2	ENST00000510534.1 link	n.65T>C	non_coding_transcript_exon_variant	Exon 1 of 3	1
DKK2	ENST00000510463.1 link	c.84+92194T>C	intron_variant	Intron 3 of 5	3		ENSP00000423797.1	D6RCC2

Frequencies

GnomAD3 genomes

AF:

0.0925

AC:

14070

AN:

152066

Hom.:

864

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0451

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.0689

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0869

Gnomad OTH

AF:

0.0951

GnomAD4 exome

AF:

0.100

AC:

53674

AN:

535426

Hom.:

3248

Cov.:

AF XY:

0.101

AC XY:

28103

AN XY:

279268

show subpopulations

Gnomad4 AFR exome

AF:

0.0405

AC:

579

AN:

14282

Gnomad4 AMR exome

AF:

0.141

AC:

2974

AN:

21166

Gnomad4 ASJ exome

AF:

0.0670

AC:

970

AN:

14480

Gnomad4 EAS exome

AF:

0.175

AC:

5537

AN:

31628

Gnomad4 SAS exome

AF:

0.121

AC:

5906

AN:

48734

Gnomad4 FIN exome

AF:

0.190

AC:

5665

AN:

29818

Gnomad4 NFE exome

AF:

0.0837

AC:

28794

AN:

344220

Gnomad4 Remaining exome

AF:

0.106

AC:

3054

AN:

28936

Heterozygous variant carriers

2585

5170

7754

10339

12924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0925

AC:

14078

AN:

152186

Hom.:

866

Cov.:

AF XY:

0.0988

AC XY:

7351

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0451

AC:

0.0450847

AN:

0.0450847

Gnomad4 AMR

AF:

0.126

AC:

0.126389

AN:

0.126389

Gnomad4 ASJ

AF:

0.0689

AC:

0.0688761

AN:

0.0688761

Gnomad4 EAS

AF:

0.231

AC:

0.230709

AN:

0.230709

Gnomad4 SAS

AF:

0.137

AC:

0.137174

AN:

0.137174

Gnomad4 FIN

AF:

0.192

AC:

0.192213

AN:

0.192213

Gnomad4 NFE

AF:

0.0869

AC:

0.0869054

AN:

0.0869054

Gnomad4 OTH

AF:

0.0959

AC:

0.0959357

AN:

0.0959357

Heterozygous variant carriers

653

1306

1958

2611

3264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0833

Hom.:

656

Bravo

AF:

0.0839

Asia WGS

AF:

0.217

AC:

756

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.63

Mutation Taster

=99/1

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

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