NM_213655.5:c.759+24938C>T

Variant names:

• chr12-779262-C-T
• rs2107613
• NM_213655.5:c.759+24938C>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+24938C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 151,966 control chromosomes in the GnomAD database, including 40,040 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 0.72 (40040 hom., cov: 31)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.891
• Publications: 5 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen, 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=-0.95).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK1	NM_213655.5	MANE Plus Clinical	c.759+24938C>T		intron	N/A	NP_998820.3	Q9H4A3-5
	WNK1	NM_018979.4	MANE Select	c.759+24938C>T		intron	N/A	NP_061852.3	Q9H4A3-1
	WNK1	NM_001184985.2		c.759+24938C>T		intron	N/A	NP_001171914.1	Q9H4A3-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK1	ENST00000340908.9	TSL:5 MANE Plus Clinical	c.759+24938C>T		intron	N/A	ENSP00000341292.5	Q9H4A3-5
	WNK1	ENST00000315939.11	TSL:1 MANE Select	c.759+24938C>T		intron	N/A	ENSP00000313059.6	Q9H4A3-1
	WNK1	ENST00000530271.6	TSL:1	c.759+24938C>T		intron	N/A	ENSP00000433548.3	Q9H4A3-7

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109514 AN: 151848 Hom.: 40022 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.721 AC: 109576 AN: 151966 Hom.: 40040 Cov.: 31 AF XY: 0.724 AC XY: 53768 AN XY: 74286

African (AFR) AF: 0.607 AC: 25123 AN: 41414

American (AMR) AF: 0.691 AC: 10541 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2387 AN: 3466

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

South Asian (SAS) AF: 0.708 AC: 3419 AN: 4828

European-Finnish (FIN) AF: 0.810 AC: 8549 AN: 10556

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52507 AN: 67952

Other (OTH) AF: 0.720 AC: 1521 AN: 2112

Alfa AF: 0.754 Hom.: 26393

Bravo AF: 0.708

Asia WGS AF: 0.735 AC: 2551 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.3
DANN	Benign	0.43
PhyloP100		0.89
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: rs2107613; hg19: chr12-888428; COSMIC: COSV60024796;