rs10821084

Variant names:

• chr9-93189340-T-A
• rs10821084
• NM_006648.4:c.681+3730T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-93189340-T-A
• chr9-93189340-T-C
• chr9-93189340-T-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.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
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 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.681+3730T>A		intron	N/A	NP_006639.3
	WNK2	NM_001282394.3		c.681+3730T>A		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.681+3730T>A		intron	N/A	ENSP00000411181.4
	WNK2	ENST00000297954.9	TSL:1	c.681+3730T>A		intron	N/A	ENSP00000297954.4
	WNK2	ENST00000432730.6	TSL:1	c.681+3730T>A		intron	N/A	ENSP00000415038.2

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

African (AFR) AF: 0.0826 AC: 3433 AN: 41540

American (AMR) AF: 0.239 AC: 3653 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3470

East Asian (EAS) AF: 0.507 AC: 2612 AN: 5156

South Asian (SAS) AF: 0.218 AC: 1052 AN: 4824

European-Finnish (FIN) AF: 0.130 AC: 1377 AN: 10590

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8949 AN: 67972

Other (OTH) AF: 0.122 AC: 258 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10821084; hg19: chr9-95951622;