rs752248130

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012242.4(DKK1):​c.452A>G​(p.Glu151Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

DKK1
NM_012242.4 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.48
Variant links:
Genes affected
DKK1 (HGNC:2891): (dickkopf WNT signaling pathway inhibitor 1) This gene encodes a member of the dickkopf family of proteins. Members of this family are secreted proteins characterized by two cysteine-rich domains that mediate protein-protein interactions. The encoded protein binds to the LRP6 co-receptor and inhibits beta-catenin-dependent Wnt signaling. This gene plays a role in embryonic development and may be important in bone formation in adults. Elevated expression of this gene has been observed in numerous human cancers and this protein may promote proliferation, invasion and growth in cancer cell lines. [provided by RefSeq, Sep 2017]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2715835).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DKK1NM_012242.4 linkc.452A>G p.Glu151Gly missense_variant Exon 3 of 4 ENST00000373970.4 NP_036374.1 O94907I1W660

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DKK1ENST00000373970.4 linkc.452A>G p.Glu151Gly missense_variant Exon 3 of 4 1 NM_012242.4 ENSP00000363081.3 O94907
DKK1ENST00000467359.5 linkn.452A>G non_coding_transcript_exon_variant Exon 2 of 2 2
DKK1ENST00000476752.1 linkn.101A>G non_coding_transcript_exon_variant Exon 2 of 3 2
DKK1ENST00000494277.5 linkn.75A>G non_coding_transcript_exon_variant Exon 2 of 4 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461846
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.084
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.59
D
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.74
T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.061
Sift
Benign
0.037
D
Sift4G
Uncertain
0.042
D
Polyphen
0.95
P
Vest4
0.33
MutPred
0.23
Loss of helix (P = 0.0104);
MVP
0.81
MPC
1.2
ClinPred
0.80
D
GERP RS
5.8
Varity_R
0.076
gMVP
0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-54076100; API