Genetic Variant NM_014421.3:c.*1019G>A (chr4-106922935-C-T) – 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.*1019G>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 0.285 in 152,024 control chromosomes in the GnomAD database, including 6,386 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 0.28 ( 6386 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DKK2
NM_014421.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.141

Publications

19 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK2	NM_014421.3 link	c.*1019G>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	ENST00000285311.8 link	c.*1019G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_014421.3	ENSP00000285311.3		Q9UBU2
ENSG00000286147	ENST00000650850.1 link	n.931+2747C>T		intron_variant	Intron 10 of 10

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43226

AN:

151906

Hom.:

6376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.197

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.260

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.285

AC:

43270

AN:

152024

Hom.:

6386

Cov.:

AF XY:

0.284

AC XY:

21073

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.357

AC:

14806

AN:

41470

American (AMR)

AF:

0.197

AC:

3012

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

941

AN:

3466

East Asian (EAS)

AF:

0.272

AC:

1402

AN:

5156

South Asian (SAS)

AF:

0.205

AC:

989

AN:

4820

European-Finnish (FIN)

AF:

0.323

AC:

3416

AN:

10574

Middle Eastern (MID)

AF:

0.202

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.263

AC:

17841

AN:

67956

Other (OTH)

AF:

0.266

AC:

563

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1584

3169

4753

6338

7922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.265

Hom.:

20576

Bravo

AF:

0.276

Asia WGS

AF:

0.227

AC:

788

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.7

(source)

DANN

Benign

0.70

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over