rs10494994

Variant names:

• chr1-215188864-G-A
• rs10494994
• NM_001017425.3:c.824-6089G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-215188864-G-A
• chr1-215188864-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017425.3(KCNK2):​c.824-6089G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,046 control chromosomes in the GnomAD database, including 2,879 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 0.17 (2879 hom., cov: 32)
• Consequence: KCNK2 NM_001017425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219
• Publications: 8 publications found

Genes affected

KCNK2 (HGNC:6277): (potassium two pore domain channel subfamily K member 2) This gene encodes one of the members of the two-pore-domain background potassium channel protein family. This type of potassium channel is formed by two homodimers that create a channel that leaks potassium out of the cell to control resting membrane potential. The channel can be opened, however, by certain anesthetics, membrane stretching, intracellular acidosis, and heat. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017425.3. 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
	KCNK2	NM_001017425.3	MANE Select	c.824-6089G>A		intron	N/A	NP_001017425.2
	KCNK2	NM_001017424.3		c.812-6089G>A		intron	N/A	NP_001017424.1
	KCNK2	NM_014217.4		c.779-6089G>A		intron	N/A	NP_055032.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK2	ENST00000444842.7	TSL:1 MANE Select	c.824-6089G>A		intron	N/A	ENSP00000394033.2
	KCNK2	ENST00000391895.6	TSL:1	c.812-6089G>A		intron	N/A	ENSP00000375765.2
	KCNK2	ENST00000391894.6	TSL:1	c.779-6089G>A		intron	N/A	ENSP00000375764.2

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26445 AN: 151928 Hom.: 2877 Cov.: 32

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.174 AC: 26438 AN: 152046 Hom.: 2879 Cov.: 32 AF XY: 0.179 AC XY: 13333 AN XY: 74322

African (AFR) AF: 0.0477 AC: 1979 AN: 41468

American (AMR) AF: 0.188 AC: 2874 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 946 AN: 3468

East Asian (EAS) AF: 0.256 AC: 1315 AN: 5146

South Asian (SAS) AF: 0.451 AC: 2170 AN: 4812

European-Finnish (FIN) AF: 0.189 AC: 1997 AN: 10594

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.215 AC: 14592 AN: 67976

Other (OTH) AF: 0.201 AC: 425 AN: 2112

Alfa AF: 0.209 Hom.: 4600

Bravo AF: 0.163

Asia WGS AF: 0.335 AC: 1162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.46
PhyloP100		-0.22
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: rs10494994; hg19: chr1-215362207;