12-865160-G-A

Variant names:

• chr12-865160-G-A
• rs11611231
• NM_213655.5:c.2190G>A
• WNK1 p.Leu730Leu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_213655.5(WNK1):​c.2190G>A​(p.Leu730Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000094 in 1,382,468 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: WNK1 NM_213655.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70
• Publications: 20 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, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• pseudohypoaldosteronism type 2C

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary sensory and autonomic neuropathy type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285704 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).

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.2190G>A	p.Leu730Leu	synonymous	Exon 9 of 28	NP_998820.3	Q9H4A3-5
	WNK1	NM_018979.4	MANE Select	c.2139+2890G>A		intron	N/A	NP_061852.3	Q9H4A3-1
	WNK1	NM_001184985.2		c.2140-2706G>A		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.2190G>A	p.Leu730Leu	synonymous	Exon 9 of 28	ENSP00000341292.5	Q9H4A3-5
	WNK1	ENST00000315939.11	TSL:1 MANE Select	c.2139+2890G>A		intron	N/A	ENSP00000313059.6	Q9H4A3-1
	WNK1	ENST00000530271.6	TSL:1	c.2140-2706G>A		intron	N/A	ENSP00000433548.3	Q9H4A3-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000152 AC: 2 AN: 131620 AF XY: 0.0000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000194

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000940 AC: 13 AN: 1382468 Hom.: 0 Cov.: 40 AF XY: 0.00000880 AC XY: 6 AN XY: 681918

African (AFR) AF: 0.00 AC: 0 AN: 31570

American (AMR) AF: 0.00 AC: 0 AN: 35586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25130

East Asian (EAS) AF: 0.00 AC: 0 AN: 35704

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00000928 AC: 10 AN: 1077892

Other (OTH) AF: 0.0000173 AC: 1 AN: 57856

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 555

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Benign	0.76
PhyloP100		3.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11611231;

hg19: chr12-974326;