dbSNP rs777268440: WNK2:p.Pro55Pro (chr9-93185094-G-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_006648.4(WNK2):c.165G>C(p.Pro55Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,858 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WNK2
NM_006648.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.602

Publications

0 publications found

Variant links:

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]

WNK2 links:

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ACMG classification

Classification was made for transcript

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=0.088).

BP6

Variant 9-93185094-G-C is Benign according to our data. Variant chr9-93185094-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3470329.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.602 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.165G>C	p.Pro55Pro	synonymous	Exon 2 of 30	NP_006639.3
	WNK2	NM_001282394.3		c.165G>C	p.Pro55Pro	synonymous	Exon 2 of 31	NP_001269323.1	Q9Y3S1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WNK2	ENST00000427277.7	TSL:5 MANE Select	c.165G>C	p.Pro55Pro	synonymous	Exon 2 of 30	ENSP00000411181.4	E9PCD1
WNK2	ENST00000297954.9	TSL:1	c.165G>C	p.Pro55Pro	synonymous	Exon 2 of 31	ENSP00000297954.4	Q9Y3S1-1
WNK2	ENST00000432730.6	TSL:1	c.165G>C	p.Pro55Pro	synonymous	Exon 1 of 29	ENSP00000415038.2	Q9Y3S1-2

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1160724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

566376

African (AFR)

AF:

0.00

AC:

AN:

23454

American (AMR)

AF:

0.00

AC:

AN:

15918

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17724

East Asian (EAS)

AF:

0.00

AC:

AN:

24250

South Asian (SAS)

AF:

0.00

AC:

AN:

46374

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3186

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

958932

Other (OTH)

AF:

0.00

AC:

AN:

45538

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150858

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73678

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41266

American (AMR)

AF:

0.00

AC:

AN:

15142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67558

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

3.5

(source)

DANN

Benign

0.51

PhyloP100

-0.60

PromoterAI

0.0076

Neutral

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over