rs11064518

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018979.4(WNK1):c.759+15A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,613,154 control chromosomes in the GnomAD database, including 1,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 414 hom., cov: 33)

Exomes 𝑓: 0.024 ( 993 hom. )

Consequence

WNK1
NM_018979.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.378

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-754339-A-C is Benign according to our data. Variant chr12-754339-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 137928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-754339-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK1	NM_213655.5 link	c.759+15A>C		intron_variant	Intron 1 of 27	ENST00000340908.9	NP_998820.3	Q9H4A3-5
WNK1	NM_018979.4 link	c.759+15A>C		intron_variant	Intron 1 of 27	ENST00000315939.11	NP_061852.3	Q9H4A3-1A5D8Z4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9 link	c.759+15A>C		intron_variant	Intron 1 of 27	5	NM_213655.5	ENSP00000341292.5		Q9H4A3-5
WNK1	ENST00000315939.11 link	c.759+15A>C		intron_variant	Intron 1 of 27	1	NM_018979.4	ENSP00000313059.6		Q9H4A3-1

Frequencies

GnomAD3 genomes

AF:

0.0532

AC:

8090

AN:

152112

Hom.:

412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0161

Gnomad FIN

AF:

0.0140

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0180

Gnomad OTH

AF:

0.0431

GnomAD3 exomes

AF:

0.0420

AC:

10422

AN:

248314

Hom.:

548

AF XY:

0.0358

AC XY:

4826

AN XY:

134924

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.0288

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.0219

Gnomad FIN exome

AF:

0.0136

Gnomad NFE exome

AF:

0.0180

Gnomad OTH exome

AF:

0.0363

GnomAD4 exome

AF:

0.0241

AC:

35263

AN:

1460924

Hom.:

993

Cov.:

AF XY:

0.0232

AC XY:

16889

AN XY:

726772

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.0286

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0225

Gnomad4 FIN exome

AF:

0.0146

Gnomad4 NFE exome

AF:

0.0174

Gnomad4 OTH exome

AF:

0.0295

GnomAD4 genome

AF:

0.0533

AC:

8112

AN:

152230

Hom.:

414

Cov.:

AF XY:

0.0526

AC XY:

3912

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.0271

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0164

Gnomad4 FIN

AF:

0.0140

Gnomad4 NFE

AF:

0.0180

Gnomad4 OTH

AF:

0.0432

Alfa

AF:

0.0173

Hom.:

Bravo

AF:

0.0635

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 02, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 02, 2018

Athena Diagnostics

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

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. -

Pseudohypoaldosteronism type 2C

Benign:1

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.55

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