chr12-800565-A-G

Variant names:

• chr12-800565-A-G
• rs12314329
• NM_213655.5:c.760-13077A>G

Variant summary

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

The NM_213655.5(WNK1):​c.760-13077A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 151,850 control chromosomes in the GnomAD database, including 1,414 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 0.12 (1414 hom., cov: 32)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK1	NM_213655.5	c.760-13077A>G		intron_variant	Intron 1 of 27	ENST00000340908.9	NP_998820.3
WNK1	NM_018979.4	c.760-13077A>G		intron_variant	Intron 1 of 27	ENST00000315939.11	NP_061852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9	c.760-13077A>G		intron_variant	Intron 1 of 27	5	NM_213655.5	ENSP00000341292.5
WNK1	ENST00000315939.11	c.760-13077A>G		intron_variant	Intron 1 of 27	1	NM_018979.4	ENSP00000313059.6

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18393 AN: 151732 Hom.: 1409 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0256

Gnomad FIN AF: 0.0840

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0829

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.121 AC: 18432 AN: 151850 Hom.: 1414 Cov.: 32 AF XY: 0.120 AC XY: 8898 AN XY: 74190

African (AFR) AF: 0.200 AC: 8292 AN: 41402

American (AMR) AF: 0.174 AC: 2662 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0261 AC: 125 AN: 4798

European-Finnish (FIN) AF: 0.0840 AC: 883 AN: 10514

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0829 AC: 5632 AN: 67914

Other (OTH) AF: 0.122 AC: 258 AN: 2108

Alfa AF: 0.101 Hom.: 1123

Bravo AF: 0.134

Asia WGS AF: 0.0330 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.6
DANN	Benign	0.63
PhyloP100		-0.23
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: rs12314329; hg19: chr12-909731;