rs10494989

Variant names:

• chr1-215014896-G-A
• rs10494989
• ENST00000391895.6:c.34+8941G>A

Variant summary

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

The ENST00000391895.6(KCNK2):​c.34+8941G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,978 control chromosomes in the GnomAD database, including 25,540 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 0.56 (25540 hom., cov: 32)
• Consequence: KCNK2 ENST00000391895.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK2	NM_001017424.3	c.34+8941G>A		intron_variant	Intron 1 of 6		NP_001017424.1
KCNK2	XM_017001249.2	c.-85+8941G>A		intron_variant	Intron 1 of 7		XP_016856738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK2	ENST00000391895.6	c.34+8941G>A		intron_variant	Intron 1 of 6	1		ENSP00000375765.2
KCNK2	ENST00000467031.5	n.34+8941G>A		intron_variant	Intron 1 of 5	1		ENSP00000420203.1
KCNK2	ENST00000486921.5	n.34+8941G>A		intron_variant	Intron 1 of 6	5		ENSP00000418706.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85060 AN: 151860 Hom.: 25499 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.560 AC: 85160 AN: 151978 Hom.: 25540 Cov.: 32 AF XY: 0.562 AC XY: 41739 AN XY: 74294

African (AFR) AF: 0.766 AC: 31793 AN: 41492

American (AMR) AF: 0.582 AC: 8891 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1598 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2717 AN: 5150

South Asian (SAS) AF: 0.783 AC: 3778 AN: 4824

European-Finnish (FIN) AF: 0.345 AC: 3646 AN: 10556

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30774 AN: 67888

Other (OTH) AF: 0.573 AC: 1211 AN: 2112

Alfa AF: 0.491 Hom.: 9960

Bravo AF: 0.581

Asia WGS AF: 0.671 AC: 2334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.9
DANN	Benign	0.59
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10494989; hg19: chr1-215188239;