9-93184969-C-T

Variant names:

• chr9-93184969-C-T
• rs1298800136
• NM_006648.4:c.40C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006648.4(WNK2):​c.40C>T​(p.Leu14Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000921 in 1,085,742 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. Synonymous variant affecting the same amino acid position (i.e. L14L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: WNK2 NM_006648.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-0.177 with no splicing effect.

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.40C>T	p.Leu14Leu	synonymous	Exon 2 of 30	NP_006639.3
	WNK2	NM_001282394.3		c.40C>T	p.Leu14Leu	synonymous	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.40C>T	p.Leu14Leu	synonymous	Exon 2 of 30	ENSP00000411181.4	E9PCD1
	WNK2	ENST00000297954.9	TSL:1	c.40C>T	p.Leu14Leu	synonymous	Exon 2 of 31	ENSP00000297954.4	Q9Y3S1-1
	WNK2	ENST00000432730.6	TSL:1	c.40C>T	p.Leu14Leu	synonymous	Exon 1 of 29	ENSP00000415038.2	Q9Y3S1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.21e-7 AC: 1 AN: 1085742 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 516162

African (AFR) AF: 0.00 AC: 0 AN: 22534

American (AMR) AF: 0.00 AC: 0 AN: 8100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13944

East Asian (EAS) AF: 0.00 AC: 0 AN: 25998

South Asian (SAS) AF: 0.00 AC: 0 AN: 21774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2900

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 925652

Other (OTH) AF: 0.00 AC: 0 AN: 43380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		-0.18
PromoterAI		-0.012	Neutral

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: rs1298800136; hg19: chr9-95947251;