Variant 9-93308387-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_006648.4(WNK2):c.6319G>A(p.Val2107Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 1,573,848 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.0051 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0037 ( 45 hom. )

Consequence

WNK2
NM_006648.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.57

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041105747).

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00368 (5229/1421524) while in subpopulation SAS AF= 0.0189 (1525/80628). AF 95% confidence interval is 0.0181. There are 45 homozygotes in gnomad4_exome. There are 2998 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 775 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNK2	NM_006648.4 linkuse as main transcript	c.6319G>A	p.Val2107Ile	missense_variant	28/30	ENST00000427277.7	NP_006639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNK2	ENST00000427277.7 linkuse as main transcript	c.6319G>A	p.Val2107Ile	missense_variant	28/30	5	NM_006648.4	ENSP00000411181	A2

Frequencies

GnomAD3 genomes

AF:

0.00509

AC:

775

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00975

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0159

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00318

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00505

AC:

955

AN:

189136

Hom.:

AF XY:

0.00622

AC XY:

629

AN XY:

101160

show subpopulations

Gnomad AFR exome

AF:

0.00893

Gnomad AMR exome

AF:

0.00207

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.0000737

Gnomad SAS exome

AF:

0.0194

Gnomad FIN exome

AF:

0.000454

Gnomad NFE exome

AF:

0.00331

Gnomad OTH exome

AF:

0.00377

GnomAD4 exome

AF:

0.00368

AC:

5229

AN:

1421524

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

2998

AN XY:

703362

show subpopulations

Gnomad4 AFR exome

AF:

0.00929

Gnomad4 AMR exome

AF:

0.00214

Gnomad4 ASJ exome

AF:

0.00397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0189

Gnomad4 FIN exome

AF:

0.000438

Gnomad4 NFE exome

AF:

0.00261

Gnomad4 OTH exome

AF:

0.00410

GnomAD4 genome

AF:

0.00509

AC:

775

AN:

152324

Hom.:

Cov.:

AF XY:

0.00532

AC XY:

396

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00972

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0159

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00318

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00342

Hom.:

Bravo

AF:

0.00501

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00775

AC:

ESP6500EA

AF:

0.00385

AC:

ExAC

AF:

0.00458

AC:

548

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

T;.

Eigen

Benign

-0.076

Eigen_PC

Benign

0.041

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.77

N;.

MutationTaster

Benign

0.96

D;D;D;D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.48

N;N

REVEL

Benign

0.038

Sift

Benign

0.23

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.68

P;B

Vest4

0.066

MVP

0.28

MPC

0.11

ClinPred

0.0079

GERP RS

3.6

Varity_R

0.051

gMVP

0.075

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over