9-93301408-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK2	NM_006648.4	MANE Select	c.6214+1259T>G		intron	N/A	NP_006639.3
	WNK2	NM_001282394.3		c.6325+1259T>G		intron	N/A	NP_001269323.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNK2	ENST00000427277.7	TSL:5 MANE Select	c.6214+1259T>G		intron	N/A	ENSP00000411181.4
	WNK2	ENST00000297954.9	TSL:1	c.6325+1259T>G		intron	N/A	ENSP00000297954.4
	WNK2	ENST00000432730.6	TSL:1	c.6214+1259T>G		intron	N/A	ENSP00000415038.2

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

African (AFR) AF: 0.164 AC: 6822 AN: 41526

American (AMR) AF: 0.0545 AC: 833 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3472

East Asian (EAS) AF: 0.153 AC: 793 AN: 5170

South Asian (SAS) AF: 0.101 AC: 486 AN: 4818

European-Finnish (FIN) AF: 0.0434 AC: 460 AN: 10604

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0393 AC: 2670 AN: 68000

Other (OTH) AF: 0.0829 AC: 175 AN: 2112

Alfa AF: 0.0539 Hom.: 205

Bravo AF: 0.0850

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.74
PhyloP100		-0.042
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16936752; hg19: chr9-96063690;