rs9804992

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018979.4(WNK1):c.2529G>A(p.Gln843Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,464 control chromosomes in the GnomAD database, including 20,405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1636 hom., cov: 29)

Exomes 𝑓: 0.16 ( 18769 hom. )

Consequence

WNK1
NM_018979.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.160

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 12-879728-G-A is Benign according to our data. Variant chr12-879728-G-A is described in ClinVar as [Benign]. Clinvar id is 261068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-879728-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK1	NM_018979.4 link	c.2529G>A	p.Gln843Gln	synonymous_variant	Exon 11 of 28	ENST00000315939.11	NP_061852.3	Q9H4A3-1A5D8Z4
WNK1	NM_213655.5 link	c.3867+1367G>A		intron_variant	Intron 12 of 27	ENST00000340908.9	NP_998820.3	Q9H4A3-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000315939.11 link	c.2529G>A	p.Gln843Gln	synonymous_variant	Exon 11 of 28	1	NM_018979.4	ENSP00000313059.6		Q9H4A3-1
WNK1	ENST00000340908.9 link	c.3867+1367G>A		intron_variant	Intron 12 of 27	5	NM_213655.5	ENSP00000341292.5		Q9H4A3-5

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22182

AN:

151540

Hom.:

1633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.0937

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.154

Gnomad OTH

AF:

0.153

GnomAD3 exomes

AF:

0.157

AC:

39484

AN:

251472

Hom.:

3286

AF XY:

0.158

AC XY:

21482

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.211

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.0831

Gnomad SAS exome

AF:

0.196

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.160

GnomAD4 exome

AF:

0.158

AC:

231110

AN:

1461806

Hom.:

18769

Cov.:

AF XY:

0.159

AC XY:

115557

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.211

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.113

Gnomad4 SAS exome

AF:

0.194

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.158

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.146

AC:

22206

AN:

151658

Hom.:

1636

Cov.:

AF XY:

0.145

AC XY:

10746

AN XY:

74094

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.194

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.0932

Gnomad4 SAS

AF:

0.182

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.154

Gnomad4 OTH

AF:

0.151

Alfa

AF:

0.156

Hom.:

3221

Bravo

AF:

0.151

Asia WGS

AF:

0.141

AC:

492

AN:

3478

EpiCase

AF:

0.153

EpiControl

AF:

0.159

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.40

DANN

Benign

0.75

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