rs10821084

Positions:

• chr9-93189340-T-A
• chr9-93189340-T-C
• chr9-93189340-T-G

Variant summary

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

The NM_006648.4(WNK2):​c.681+3730T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,158 control chromosomes in the GnomAD database, including 2,248 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 0.15 (2248 hom., cov: 32)
• Consequence: WNK2 NM_006648.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNK2	NM_006648.4	c.681+3730T>A		intron_variant		ENST00000427277.7	NP_006639.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNK2	ENST00000427277.7	c.681+3730T>A		intron_variant		5	NM_006648.4	ENSP00000411181	A2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22145 AN: 152040 Hom.: 2246 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.146 AC: 22144 AN: 152158 Hom.: 2248 Cov.: 32 AF XY: 0.150 AC XY: 11141 AN XY: 74372

Gnomad4 AFR AF: 0.0826

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0497 Hom.: 45

Bravo AF: 0.154

Asia WGS AF: 0.290 AC: 1012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs10821084; hg19: chr9-95951622;