rs10992674

Positions:

• chr9-93200832-G-A

Variant summary

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

The NM_006648.4(WNK2):​c.681+15222G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,034 control chromosomes in the GnomAD database, including 26,130 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 0.58 (26130 hom., cov: 32)
• Consequence: WNK2 NM_006648.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNK2	NM_006648.4	c.681+15222G>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+15222G>A		intron_variant		5	NM_006648.4	ENSP00000411181	A2

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87949 AN: 151916 Hom.: 26108 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.579 AC: 88008 AN: 152034 Hom.: 26130 Cov.: 32 AF XY: 0.575 AC XY: 42718 AN XY: 74308

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.575

Alfa AF: 0.632 Hom.: 49216

Bravo AF: 0.574

Asia WGS AF: 0.540 AC: 1880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.64

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: rs10992674; hg19: chr9-95963114;