rs2051852

Variant names:

• chr12-892853-G-A
• rs2051852
• NM_213655.5:c.6266-1709G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-892853-G-A
• chr12-892853-G-C

Variant summary

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

The NM_213655.5(WNK1):​c.6266-1709G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,048 control chromosomes in the GnomAD database, including 7,668 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 0.30 (7668 hom., cov: 31)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• 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: 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK1	NM_213655.5	c.6266-1709G>A		intron_variant	Intron 22 of 27	ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4	c.5510-1709G>A		intron_variant	Intron 22 of 27	ENST00000315939.11	NP_061852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9	c.6266-1709G>A		intron_variant	Intron 22 of 27	5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11	c.5510-1709G>A		intron_variant	Intron 22 of 27	1	NM_018979.4	ENSP00000313059.6

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46168 AN: 151930 Hom.: 7660 Cov.: 31

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.304 AC: 46218 AN: 152048 Hom.: 7668 Cov.: 31 AF XY: 0.301 AC XY: 22338 AN XY: 74332

African (AFR) AF: 0.441 AC: 18263 AN: 41442

American (AMR) AF: 0.259 AC: 3965 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1110 AN: 3470

East Asian (EAS) AF: 0.197 AC: 1019 AN: 5162

South Asian (SAS) AF: 0.322 AC: 1549 AN: 4816

European-Finnish (FIN) AF: 0.187 AC: 1981 AN: 10584

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17425 AN: 67968

Other (OTH) AF: 0.320 AC: 677 AN: 2114

Alfa AF: 0.284 Hom.: 858

Bravo AF: 0.313

Asia WGS AF: 0.297 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.031
DANN	Benign	0.31
PhyloP100		-1.4
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: rs2051852; hg19: chr12-1002019;