Variant rs72647375 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_213655.5(WNK1):c.759+16_759+18dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 1,613,104 control chromosomes in the GnomAD database, including 3,750 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 660 hom., cov: 32)

Exomes 𝑓: 0.061 ( 3090 hom. )

Consequence

WNK1
NM_213655.5 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.0360

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 -16 ACMG points.

BP6

Variant 12-754339-A-ACTT is Benign according to our data. Variant chr12-754339-A-ACTT is described in ClinVar as [Benign]. Clinvar id is 310547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNK1	NM_018979.4 linkuse as main transcript	c.759+16_759+18dup		intron_variant		ENST00000315939.11
WNK1	NM_213655.5 linkuse as main transcript	c.759+16_759+18dup		intron_variant		ENST00000340908.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNK1	ENST00000315939.11 linkuse as main transcript	c.759+16_759+18dup		intron_variant		1	NM_018979.4	P2	Q9H4A3-1
WNK1	ENST00000340908.9 linkuse as main transcript	c.759+16_759+18dup		intron_variant		5	NM_213655.5	A2	Q9H4A3-5

Frequencies

GnomAD3 genomes

AF:

0.0835

AC:

12692

AN:

152090

Hom.:

659

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.131

Gnomad AMR

AF:

0.0689

Gnomad ASJ

AF:

0.0916

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.0696

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0641

Gnomad OTH

AF:

0.0882

GnomAD3 exomes

AF:

0.0576

AC:

14315

AN:

248314

Hom.:

592

AF XY:

0.0554

AC XY:

7479

AN XY:

134924

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.0426

Gnomad ASJ exome

AF:

0.0953

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00912

Gnomad FIN exome

AF:

0.0706

Gnomad NFE exome

AF:

0.0670

Gnomad OTH exome

AF:

0.0563

GnomAD4 exome

AF:

0.0607

AC:

88675

AN:

1460896

Hom.:

3090

Cov.:

AF XY:

0.0594

AC XY:

43168

AN XY:

726760

show subpopulations

Gnomad4 AFR exome

AF:

0.143

Gnomad4 AMR exome

AF:

0.0460

Gnomad4 ASJ exome

AF:

0.0929

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0104

Gnomad4 FIN exome

AF:

0.0653

Gnomad4 NFE exome

AF:

0.0640

Gnomad4 OTH exome

AF:

0.0607

GnomAD4 genome

AF:

0.0835

AC:

12712

AN:

152208

Hom.:

660

Cov.:

AF XY:

0.0821

AC XY:

6111

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.0687

Gnomad4 ASJ

AF:

0.0916

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00952

Gnomad4 FIN

AF:

0.0696

Gnomad4 NFE

AF:

0.0640

Gnomad4 OTH

AF:

0.0878

Alfa

AF:

0.0761

Hom.:

Bravo

AF:

0.0874

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 06, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jan 16, 2018

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 10, 2019

- -

Pseudohypoaldosteronism type 2A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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