10-52316562-G-A
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_012242.4(DKK1):c.556G>A(p.Gly186Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
DKK1
NM_012242.4 missense
NM_012242.4 missense
Scores
2
10
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.41
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DKK1 | ENST00000373970.4 | c.556G>A | p.Gly186Ser | missense_variant | Exon 4 of 4 | 1 | NM_012242.4 | ENSP00000363081.3 | ||
DKK1 | ENST00000476752.1 | n.205G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 | |||||
DKK1 | ENST00000494277.5 | n.179G>A | non_coding_transcript_exon_variant | Exon 3 of 4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461652Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727108
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74350
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
T
Polyphen
P
Vest4
MutPred
Gain of disorder (P = 0.0521);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at