rs1369815144

Variant names:

• chr9-93184967-C-A
• rs1369815144
• NM_006648.4:c.38C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-93184967-C-A
• chr9-93184967-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_006648.4(WNK2):​c.38C>A​(p.Thr13Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000461 in 1,084,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. T13M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: WNK2 NM_006648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.632
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10317221).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.38C>A	p.Thr13Lys	missense	Exon 2 of 30	NP_006639.3
	WNK2	NM_001282394.3		c.38C>A	p.Thr13Lys	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.38C>A	p.Thr13Lys	missense	Exon 2 of 30	ENSP00000411181.4	E9PCD1
	WNK2	ENST00000297954.9	TSL:1	c.38C>A	p.Thr13Lys	missense	Exon 2 of 31	ENSP00000297954.4	Q9Y3S1-1
	WNK2	ENST00000432730.6	TSL:1	c.38C>A	p.Thr13Lys	missense	Exon 1 of 29	ENSP00000415038.2	Q9Y3S1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000461 AC: 5 AN: 1084880 Hom.: 0 Cov.: 31 AF XY: 0.00000388 AC XY: 2 AN XY: 515594

African (AFR) AF: 0.00 AC: 0 AN: 22500

American (AMR) AF: 0.00 AC: 0 AN: 8098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13934

East Asian (EAS) AF: 0.00 AC: 0 AN: 25976

South Asian (SAS) AF: 0.00 AC: 0 AN: 21688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2898

European-Non Finnish (NFE) AF: 0.00000541 AC: 5 AN: 924992

Other (OTH) AF: 0.00 AC: 0 AN: 43346

GnomAD4 genome Cov.: 32

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	Benign	0.21
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Benign	0.92
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.68	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.63
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.11
Sift	Uncertain	0.010	D
Sift4G	Benign	0.10	T
Polyphen		0.0	B
Vest4		0.083
MutPred		0.19		Gain of ubiquitination at T13 (P = 0.0045)
MVP		0.068
MPC		1.7
ClinPred		0.081	T
GERP RS		0.86
PromoterAI		0.071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.077
gMVP		0.29
Mutation Taster		=300/0	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: rs1369815144; hg19: chr9-95947249;