NM_006648.4:c.213G>C

Variant names:

• chr9-93185142-G-C
• rs1404350753
• NM_006648.4:c.213G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_006648.4(WNK2):​c.213G>C​(p.Leu71Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000261 in 1,148,800 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L71L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: WNK2 NM_006648.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.460
• 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 (REVEL=0.077).
• BP6: Variant 9-93185142-G-C is Benign according to our data. Variant chr9-93185142-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3470162.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.46 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.213G>C	p.Leu71Leu	synonymous	Exon 2 of 30	NP_006639.3
	WNK2	NM_001282394.3		c.213G>C	p.Leu71Leu	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.213G>C	p.Leu71Leu	synonymous	Exon 2 of 30	ENSP00000411181.4	E9PCD1
	WNK2	ENST00000297954.9	TSL:1	c.213G>C	p.Leu71Leu	synonymous	Exon 2 of 31	ENSP00000297954.4	Q9Y3S1-1
	WNK2	ENST00000432730.6	TSL:1	c.213G>C	p.Leu71Leu	synonymous	Exon 1 of 29	ENSP00000415038.2	Q9Y3S1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000261 AC: 3 AN: 1148800 Hom.: 0 Cov.: 31 AF XY: 0.00000357 AC XY: 2 AN XY: 560470

African (AFR) AF: 0.00 AC: 0 AN: 22948

American (AMR) AF: 0.00 AC: 0 AN: 16068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17268

East Asian (EAS) AF: 0.00 AC: 0 AN: 22898

South Asian (SAS) AF: 0.00 AC: 0 AN: 47290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3102

European-Non Finnish (NFE) AF: 0.00000316 AC: 3 AN: 950026

Other (OTH) AF: 0.00 AC: 0 AN: 44568

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		0.46
PromoterAI		0.0012	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: rs1404350753; hg19: chr9-95947424;