rs2369402

Variant names:

• chr12-769498-A-G
• rs2369402
• NM_213655.5:c.759+15174A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-769498-A-G
• chr12-769498-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_213655.5(WNK1):​c.759+15174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,222 control chromosomes in the GnomAD database, including 45,935 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (45935 hom., cov: 33)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213655.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK1	NM_213655.5	MANE Plus Clinical	c.759+15174A>G		intron	N/A	NP_998820.3
	WNK1	NM_018979.4	MANE Select	c.759+15174A>G		intron	N/A	NP_061852.3
	WNK1	NM_001184985.2		c.759+15174A>G		intron	N/A	NP_001171914.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK1	ENST00000340908.9	TSL:5 MANE Plus Clinical	c.759+15174A>G		intron	N/A	ENSP00000341292.5
	WNK1	ENST00000315939.11	TSL:1 MANE Select	c.759+15174A>G		intron	N/A	ENSP00000313059.6
	WNK1	ENST00000530271.6	TSL:1	c.759+15174A>G		intron	N/A	ENSP00000433548.3

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117953 AN: 152104 Hom.: 45905 Cov.: 33

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.767

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.775 AC: 118038 AN: 152222 Hom.: 45935 Cov.: 33 AF XY: 0.778 AC XY: 57895 AN XY: 74426

African (AFR) AF: 0.719 AC: 29854 AN: 41516

American (AMR) AF: 0.803 AC: 12259 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2492 AN: 3468

East Asian (EAS) AF: 0.872 AC: 4523 AN: 5184

South Asian (SAS) AF: 0.760 AC: 3668 AN: 4828

European-Finnish (FIN) AF: 0.823 AC: 8728 AN: 10604

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53859 AN: 68026

Other (OTH) AF: 0.763 AC: 1613 AN: 2114

Alfa AF: 0.754 Hom.: 5564

Bravo AF: 0.773

Asia WGS AF: 0.773 AC: 2685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.71
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2369402; hg19: chr12-878664;