rs2286006

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_213655.5(WNK1):c.1479T>C(p.Asp493Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,612,990 control chromosomes in the GnomAD database, including 19,482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1489 hom., cov: 31)

Exomes 𝑓: 0.15 ( 17993 hom. )

Consequence

WNK1
NM_213655.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.615

Publications

18 publications found

Variant links:

Genes affected

WNK1 (HGNC:14540): (WNK lysine deficient protein kinase 1) This gene encodes a member of the WNK subfamily of serine/threonine protein kinases. The encoded protein may be a key regulator of blood pressure by controlling the transport of sodium and chloride ions. Mutations in this gene have been associated with pseudohypoaldosteronism type II and hereditary sensory neuropathy type II. Alternatively spliced transcript variants encoding different isoforms have been described but the full-length nature of all of them has yet to be determined.[provided by RefSeq, May 2010]

WNK1 Gene-Disease associations (from GenCC):

neuropathy, hereditary sensory and autonomic, type 2A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics
pseudohypoaldosteronism type 2C
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
hereditary sensory and autonomic neuropathy type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

WNK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 12-859323-T-C is Benign according to our data. Variant chr12-859323-T-C is described in ClinVar as Benign. ClinVar VariationId is 137923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.615 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK1	NM_213655.5 link	c.1479T>C	p.Asp493Asp	synonymous_variant	Exon 6 of 28	ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4 link	c.1479T>C	p.Asp493Asp	synonymous_variant	Exon 6 of 28	ENST00000315939.11	NP_061852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9 link	c.1479T>C	p.Asp493Asp	synonymous_variant	Exon 6 of 28	5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11 link	c.1479T>C	p.Asp493Asp	synonymous_variant	Exon 6 of 28	1	NM_018979.4	ENSP00000313059.6

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19086

AN:

151916

Hom.:

1488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0504

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.0900

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.0614

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.122

GnomAD2 exomes

AF:

0.146

AC:

36681

AN:

250580

AF XY:

0.154

show subpopulations

Gnomad AFR exome

AF:

0.0473

Gnomad AMR exome

AF:

0.0692

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.0672

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.160

GnomAD4 exome

AF:

0.151

AC:

220517

AN:

1460956

Hom.:

17993

Cov.:

AF XY:

0.153

AC XY:

111195

AN XY:

726800

show subpopulations

African (AFR)

AF:

0.0455

AC:

1521

AN:

33464

American (AMR)

AF:

0.0713

AC:

3186

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

3994

AN:

26124

East Asian (EAS)

AF:

0.0488

AC:

1933

AN:

39628

South Asian (SAS)

AF:

0.185

AC:

15981

AN:

86220

European-Finnish (FIN)

AF:

0.266

AC:

14172

AN:

53370

Middle Eastern (MID)

AF:

0.205

AC:

1181

AN:

5760

European-Non Finnish (NFE)

AF:

0.153

AC:

169582

AN:

1111316

Other (OTH)

AF:

0.149

AC:

8967

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

8950

17899

26849

35798

44748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5942

11884

17826

23768

29710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.126

AC:

19098

AN:

152034

Hom.:

1489

Cov.:

AF XY:

0.130

AC XY:

9659

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0506

AC:

2101

AN:

41486

American (AMR)

AF:

0.0899

AC:

1373

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

534

AN:

3468

East Asian (EAS)

AF:

0.0615

AC:

318

AN:

5170

South Asian (SAS)

AF:

0.170

AC:

819

AN:

4828

European-Finnish (FIN)

AF:

0.273

AC:

2875

AN:

10534

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.156

AC:

10584

AN:

67968

Other (OTH)

AF:

0.121

AC:

254

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

817

1633

2450

3266

4083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.143

Hom.:

5588

Bravo

AF:

0.107

Asia WGS

AF:

0.107

AC:

371

AN:

3476

EpiCase

AF:

0.154

EpiControl

AF:

0.159

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Mar 07, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Neuropathy, hereditary sensory and autonomic, type 2A

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jun 12, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Pseudohypoaldosteronism type 2C

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.6

(source)

DANN

Benign

0.52

PhyloP100

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over