rs2277869

chr12-907744-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_213655.5(WNK1):c.7400-103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,360,380 control chromosomes in the GnomAD database, including 17,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (1886 hom., cov: 32)
  • Exomes 𝑓: 0.16 (15891 hom.)
• Consequence: WNK1 NM_213655.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.237

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 12-907744-T-C is Benign according to our data. Variant chr12-907744-T-C is described in ClinVar as [Benign]. Clinvar id is 1229228.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNK1	NM_018979.4	c.6644-103T>C		intron_variant		ENST00000315939.11
WNK1	NM_213655.5	c.7400-103T>C		intron_variant		ENST00000340908.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNK1	ENST00000315939.11	c.6644-103T>C		intron_variant		1	NM_018979.4	P2
WNK1	ENST00000340908.9	c.7400-103T>C		intron_variant		5	NM_213655.5	A2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23972 AN: 152130 Hom.: 1881 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0939

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.160 AC: 193302 AN: 1208132 Hom.: 15891 Cov.: 17 AF XY: 0.161 AC XY: 98630 AN XY: 613550

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.158 AC: 24002 AN: 152248 Hom.: 1886 Cov.: 32 AF XY: 0.156 AC XY: 11597 AN XY: 74440

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0935

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.161

Alfa AF: 0.160 Hom.: 361

Bravo AF: 0.163

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	12
Dann	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs2277869; hg19: chr12-1016910; COSMIC: COSV57272285; COSMIC: COSV57272285;