chr9-93184996-C-A

Variant summary

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

The NM_006648.4(WNK2):​c.67C>A​(p.Pro23Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 149,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

WNK2
NM_006648.4 missense

Scores

2
1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.49
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]

Genome browser will be placed here

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=0.08331406).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WNK2NM_006648.4 linkc.67C>A p.Pro23Thr 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.67C>A p.Pro23Thr missense_variant Exon 2 of 30 5 NM_006648.4 ENSP00000411181.4 E9PCD1

Frequencies

GnomAD3 genomes
AF:
0.0000200
AC:
3
AN:
149772
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000736
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1093170
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
522106
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000200
AC:
3
AN:
149772
Hom.:
0
Cov.:
32
AF XY:
0.0000273
AC XY:
2
AN XY:
73164
show subpopulations
Gnomad4 AFR
AF:
0.0000736
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
20
DANN
Benign
0.90
DEOGEN2
Benign
0.032
.;T;.
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.73
T;T;T
M_CAP
Pathogenic
0.51
D
MetaRNN
Benign
0.083
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;L;.
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-0.72
N;N;N
REVEL
Benign
0.063
Sift
Uncertain
0.027
D;D;D
Sift4G
Benign
0.76
T;T;T
Polyphen
0.063, 0.10
.;B;B
Vest4
0.047, 0.090
MutPred
0.22
Gain of phosphorylation at P23 (P = 0.0178);Gain of phosphorylation at P23 (P = 0.0178);Gain of phosphorylation at P23 (P = 0.0178);
MVP
0.082
MPC
1.6
ClinPred
0.044
T
GERP RS
-3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.057
gMVP
0.47

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: rs1371549502; hg19: chr9-95947278; API