Variant rs35706572 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 8P and 16B. PVS1BP6_Very_StrongBA1

The NM_213655.5(WNK1):c.2175dupC(p.Ile726fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,531,260 control chromosomes in the GnomAD database, including 62,024 homozygotes. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.26 ( 5511 hom., cov: 21)

Exomes 𝑓: 0.28 ( 56513 hom. )

Consequence

WNK1
NM_213655.5 frameshift

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 7.43

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 -8 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

BP6

Variant 12-865142-T-TC is Benign according to our data. Variant chr12-865142-T-TC is described in ClinVar as [Benign]. Clinvar id is 1166421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNK1	NM_213655.5 linkuse as main transcript	c.2175dupC	p.Ile726fs	frameshift_variant	9/28	ENST00000340908.9	NP_998820.3	Q9H4A3-5
WNK1	NM_018979.4 linkuse as main transcript	c.2139+2875dupC		intron_variant		ENST00000315939.11	NP_061852.3	Q9H4A3-1A5D8Z4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9 linkuse as main transcript	c.2175dupC	p.Ile726fs	frameshift_variant	9/28	5	NM_213655.5	ENSP00000341292.5		Q9H4A3-5
WNK1	ENST00000315939.11 linkuse as main transcript	c.2139+2875dupC		intron_variant		1	NM_018979.4	ENSP00000313059.6		Q9H4A3-1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39874

AN:

151880

Hom.:

5509

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.284

GnomAD3 exomes

AF:

0.248

AC:

32097

AN:

129242

Hom.:

4692

AF XY:

0.254

AC XY:

17815

AN XY:

70252

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.423

Gnomad EAS exome

AF:

0.102

Gnomad SAS exome

AF:

0.243

Gnomad FIN exome

AF:

0.240

Gnomad NFE exome

AF:

0.297

Gnomad OTH exome

AF:

0.311

GnomAD4 exome

AF:

0.282

AC:

389156

AN:

1379262

Hom.:

56513

Cov.:

AF XY:

0.283

AC XY:

192336

AN XY:

679836

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.172

Gnomad4 ASJ exome

AF:

0.433

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.247

Gnomad4 FIN exome

AF:

0.247

Gnomad4 NFE exome

AF:

0.291

Gnomad4 OTH exome

AF:

0.286

GnomAD4 genome

AF:

0.262

AC:

39891

AN:

151998

Hom.:

5511

Cov.:

AF XY:

0.259

AC XY:

19214

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.228

Gnomad4 AMR

AF:

0.219

Gnomad4 ASJ

AF:

0.440

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.251

Gnomad4 NFE

AF:

0.296

Gnomad4 OTH

AF:

0.282

Alfa

AF:

0.295

Hom.:

1535

Bravo

AF:

0.259

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over