chr9-93184984-C-A

Variant names:

• chr9-93184984-C-A
• rs1343202924
• NM_006648.4:c.55C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006648.4(WNK2):​c.55C>A​(p.Arg19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,240,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R19C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: WNK2 NM_006648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.317
• Publications: 0 publications found

Genes affected

WNK2 (HGNC:14542): (WNK lysine deficient protein kinase 2) The protein encoded by this gene is a cytoplasmic serine-threonine kinase that belongs to the protein kinase superfamily. The protein plays an important role in the regulation of electrolyte homeostasis, cell signaling survival, and proliferation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1976211).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006648.4. 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
	WNK2	NM_006648.4	MANE Select	c.55C>A	p.Arg19Ser	missense	Exon 2 of 30	NP_006639.3
	WNK2	NM_001282394.3		c.55C>A	p.Arg19Ser	missense	Exon 2 of 31	NP_001269323.1	Q9Y3S1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK2	ENST00000427277.7	TSL:5 MANE Select	c.55C>A	p.Arg19Ser	missense	Exon 2 of 30	ENSP00000411181.4	E9PCD1
	WNK2	ENST00000297954.9	TSL:1	c.55C>A	p.Arg19Ser	missense	Exon 2 of 31	ENSP00000297954.4	Q9Y3S1-1
	WNK2	ENST00000432730.6	TSL:1	c.55C>A	p.Arg19Ser	missense	Exon 1 of 29	ENSP00000415038.2	Q9Y3S1-2

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151688 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.18e-7 AC: 1 AN: 1088750 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 518606

African (AFR) AF: 0.0000444 AC: 1 AN: 22510

American (AMR) AF: 0.00 AC: 0 AN: 8112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13908

East Asian (EAS) AF: 0.00 AC: 0 AN: 25938

South Asian (SAS) AF: 0.00 AC: 0 AN: 22112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2906

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 928270

Other (OTH) AF: 0.00 AC: 0 AN: 43500

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151688 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74090

African (AFR) AF: 0.0000242 AC: 1 AN: 41360

American (AMR) AF: 0.00 AC: 0 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67852

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.32
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.053
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.25	T
Polyphen		0.15	B
Vest4		0.097
MutPred		0.31		Gain of glycosylation at R19 (P = 7e-04)
MVP		0.082
MPC		1.6
ClinPred		0.48	T
GERP RS		2.0
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.25
gMVP		0.52
Mutation Taster		=91/9	polymorphism

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: rs1343202924; hg19: chr9-95947266;