rs16936752

Variant names:

• chr9-93301408-T-G
• rs16936752
• NM_006648.4:c.6214+1259T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006648.4(WNK2):​c.6214+1259T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 152,202 control chromosomes in the GnomAD database, including 769 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.083 (769 hom., cov: 32)
• Consequence: WNK2 NM_006648.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK2	NM_006648.4	c.6214+1259T>G		intron_variant	Intron 26 of 29	ENST00000427277.7	NP_006639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK2	ENST00000427277.7	c.6214+1259T>G		intron_variant	Intron 26 of 29	5	NM_006648.4	ENSP00000411181.4

Frequencies

GnomAD3 genomes AF: 0.0825 AC: 12554 AN: 152084 Hom.: 759 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0434

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.0818

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0827 AC: 12593 AN: 152202 Hom.: 769 Cov.: 32 AF XY: 0.0818 AC XY: 6088 AN XY: 74404

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0545

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0434

Gnomad4 NFE AF: 0.0393

Gnomad4 OTH AF: 0.0829

Alfa AF: 0.0526 Hom.: 139

Bravo AF: 0.0850

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16936752; hg19: chr9-96063690;