9-93185094-G-A

Variant names:

• chr9-93185094-G-A
• rs777268440
• NM_006648.4:c.165G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Moderate BP7 BS2

The NM_006648.4(WNK2):​c.165G>A​(p.Pro55Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000431 in 1,160,724 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. P55P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: WNK2 NM_006648.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.088).
• BP7: Synonymous conserved (PhyloP=-0.602 with no splicing effect.
• 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.165G>A	p.Pro55Pro	synonymous	Exon 2 of 30	NP_006639.3
	WNK2	NM_001282394.3		c.165G>A	p.Pro55Pro	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.165G>A	p.Pro55Pro	synonymous	Exon 2 of 30	ENSP00000411181.4	E9PCD1
	WNK2	ENST00000297954.9	TSL:1	c.165G>A	p.Pro55Pro	synonymous	Exon 2 of 31	ENSP00000297954.4	Q9Y3S1-1
	WNK2	ENST00000432730.6	TSL:1	c.165G>A	p.Pro55Pro	synonymous	Exon 1 of 29	ENSP00000415038.2	Q9Y3S1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000395 AC: 2 AN: 50634 AF XY: 0.0000647

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000431 AC: 5 AN: 1160724 Hom.: 0 Cov.: 31 AF XY: 0.00000530 AC XY: 3 AN XY: 566376

African (AFR) AF: 0.00 AC: 0 AN: 23454

American (AMR) AF: 0.00 AC: 0 AN: 15918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17724

East Asian (EAS) AF: 0.00 AC: 0 AN: 24250

South Asian (SAS) AF: 0.000108 AC: 5 AN: 46374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3186

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 958932

Other (OTH) AF: 0.00 AC: 0 AN: 45538

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.8
DANN	Benign	0.90
PhyloP100		-0.60
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: rs777268440; hg19: chr9-95947376;