Variant 9-93185138-C-A 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.209C>A(p.Pro70His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000956 in 1,150,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

WNK2
NM_006648.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0240

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24626595).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNK2	NM_006648.4 link	c.209C>A	p.Pro70His	missense_variant	2/30	ENST00000427277.7	NP_006639.3	E9PCD1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNK2	ENST00000427277.7 link	c.209C>A	p.Pro70His	missense_variant	2/30	5	NM_006648.4	ENSP00000411181.4		E9PCD1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000956

AC:

AN:

1150386

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

561290

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:

0.0000116

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2024

The p.P70H variant (also known as c.209C>A), located in coding exon 1 of the WNK2 gene, results from a C to A substitution at nucleotide position 209. The proline at codon 70 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

.;T;.

Eigen

Benign

-0.091

Eigen_PC

Benign

-0.069

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.70

T;T;T

M_CAP

Pathogenic

0.92

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.8

.;L;.

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.021

D;D;D

Polyphen

0.99, 0.99

.;D;D

Vest4

0.11, 0.32

MutPred

0.17

Loss of glycosylation at P70 (P = 0.0064);Loss of glycosylation at P70 (P = 0.0064);Loss of glycosylation at P70 (P = 0.0064);

MVP

0.13

MPC

1.6

ClinPred

0.94

GERP RS

2.1

Varity_R

0.39

gMVP

0.30

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over