Variant 9-93185079-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006648.4(WNK2):c.150C>G(p.Asp50Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000608 in 1,315,052 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000060 ( 0 hom. )

Consequence

WNK2
NM_006648.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.236

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]

WNK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16808274).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK2	NM_006648.4 link	c.150C>G	p.Asp50Glu	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
WNK2	ENST00000427277.7 link	c.150C>G	p.Asp50Glu	missense_variant	Exon 2 of 30	5	NM_006648.4	ENSP00000411181.4		E9PCD1

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000411

AC:

AN:

48684

Hom.:

AF XY:

0.00

AC XY:

AN XY:

29900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000220

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000707

GnomAD4 exome

AF:

0.00000601

AC:

AN:

1164134

Hom.:

Cov.:

AF XY:

0.00000528

AC XY:

AN XY:

568480

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000282

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:

0.0000437

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150918

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73702

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.150C>G (p.D50E) alteration is located in exon 1 (coding exon 1) of the WNK2 gene. This alteration results from a C to G substitution at nucleotide position 150, causing the aspartic acid (D) at amino acid position 50 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.051

.;T;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.72

T;T;T

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;L;.

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.070

T;D;D

Sift4G

Benign

0.14

T;D;D

Polyphen

0.90, 0.94

.;P;P

Vest4

0.036, 0.10

MutPred

0.077

Gain of glycosylation at P55 (P = 0.1223);Gain of glycosylation at P55 (P = 0.1223);Gain of glycosylation at P55 (P = 0.1223);

MVP

0.22

MPC

1.3

ClinPred

0.087

GERP RS

-0.29

Varity_R

0.098

gMVP

0.26

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over