chr9-93184957-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006648.4(WNK2):​c.28G>A​(p.Val10Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000927 in 1,079,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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: 32)
Exomes 𝑓: 9.3e-7 ( 0 hom. )

Consequence

WNK2
NM_006648.4 missense

Scores

2
2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.809
Variant links:
Genes affected
WNK2 (HGNC:14542): (WNK lysine deficient protein kinase 2) The protein encoded by this gene is a cytoplasmic serine-threonine kinase that belongs to the protein kinase superfamily. The protein plays an important role in the regulation of electrolyte homeostasis, cell signaling survival, and proliferation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08050385).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WNK2NM_006648.4 linkc.28G>A p.Val10Ile missense_variant Exon 2 of 30 ENST00000427277.7 NP_006639.3 E9PCD1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WNK2ENST00000427277.7 linkc.28G>A p.Val10Ile missense_variant Exon 2 of 30 5 NM_006648.4 ENSP00000411181.4 E9PCD1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
9.27e-7
AC:
1
AN:
1079318
Hom.:
0
Cov.:
31
AF XY:
0.00000195
AC XY:
1
AN XY:
512302
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:
0.00000109
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.033
.;T;.
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.60
T;T;T
M_CAP
Pathogenic
0.38
D
MetaRNN
Benign
0.081
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.0
.;N;.
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-0.21
N;N;N
REVEL
Benign
0.20
Sift
Uncertain
0.019
D;D;D
Sift4G
Benign
0.61
T;T;T
Polyphen
0.0, 0.0010
.;B;B
Vest4
0.045, 0.067
MutPred
0.050
Loss of methylation at R7 (P = 0.1351);Loss of methylation at R7 (P = 0.1351);Loss of methylation at R7 (P = 0.1351);
MVP
0.043
MPC
1.2
ClinPred
0.16
T
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.10
gMVP
0.097

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.

Other links and lift over

dbSNP: rs1200556186; hg19: chr9-95947239; API