9-93185416-C-T

Position:

• chr9-93185416-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006648.4(WNK2):​c.487C>T​(p.Pro163Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WNK2 NM_006648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.557

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1764924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNK2	NM_006648.4	c.487C>T	p.Pro163Ser	missense_variant	2/30	ENST00000427277.7	NP_006639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNK2	ENST00000427277.7	c.487C>T	p.Pro163Ser	missense_variant	2/30	5	NM_006648.4	ENSP00000411181	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2022

The c.487C>T (p.P163S) alteration is located in exon 1 (coding exon 1) of the WNK2 gene. This alteration results from a C to T substitution at nucleotide position 487, causing the proline (P) at amino acid position 163 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	.;T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.9	.;L;.
MutationTaster	Benign	1.0	D;D;D;N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.086	T;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.73, 0.46	.;P;P
Vest4		0.10, 0.14
MutPred		0.16		Gain of phosphorylation at P163 (P = 0.0033);Gain of phosphorylation at P163 (P = 0.0033);Gain of phosphorylation at P163 (P = 0.0033);
MVP		0.23
MPC		1.4
ClinPred		0.49	T
GERP RS		3.3
Varity_R		0.092
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-95947698;