rs1271299696

Variant names:

• chr9-93185115-G-A
• rs1271299696
• NM_006648.4:c.186G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-93185115-G-A
• chr9-93185115-G-C
• chr9-93185115-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006648.4(WNK2):​c.186G>A​(p.Ala62Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,158,264 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. A62A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: WNK2 NM_006648.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.013).

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.186G>A	p.Ala62Ala	synonymous	Exon 2 of 30	NP_006639.3
	WNK2	NM_001282394.3		c.186G>A	p.Ala62Ala	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.186G>A	p.Ala62Ala	synonymous	Exon 2 of 30	ENSP00000411181.4	E9PCD1
	WNK2	ENST00000297954.9	TSL:1	c.186G>A	p.Ala62Ala	synonymous	Exon 2 of 31	ENSP00000297954.4	Q9Y3S1-1
	WNK2	ENST00000432730.6	TSL:1	c.186G>A	p.Ala62Ala	synonymous	Exon 1 of 29	ENSP00000415038.2	Q9Y3S1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000345 AC: 4 AN: 1158264 Hom.: 0 Cov.: 31 AF XY: 0.00000531 AC XY: 3 AN XY: 565178

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23348

American (AMR) AF: 0.00 AC: 0 AN: 16442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17662

East Asian (EAS) AF: 0.00 AC: 0 AN: 23746

South Asian (SAS) AF: 0.0000212 AC: 1 AN: 47196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3184

European-Non Finnish (NFE) AF: 0.00000314 AC: 3 AN: 956270

Other (OTH) AF: 0.00 AC: 0 AN: 45240

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.7
DANN	Benign	0.94
PhyloP100		0.17
PromoterAI		0.0068	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: rs1271299696; hg19: chr9-95947397;