rs2802643

chr1-215024279-A-Cchr1-215024279-A-Gchr1-215024279-A-T

Variant summary

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

The ENST00000391895.6(KCNK2):c.34+18324A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,758 control chromosomes in the GnomAD database, including 16,206 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 0.44 (16206 hom., cov: 32)
• Consequence: KCNK2 ENST00000391895.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.57

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK2	NM_001017424.3	c.34+18324A>C		intron_variant
KCNK2	XM_017001249.2	c.-84-11988A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK2	ENST00000391895.6	c.34+18324A>C		intron_variant		1
KCNK2	ENST00000467031.5	c.34+18324A>C		intron_variant, NMD_transcript_variant		1
KCNK2	ENST00000486921.5	c.34+18324A>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66479 AN: 151640 Hom.: 16206 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.438 AC: 66497 AN: 151758 Hom.: 16206 Cov.: 32 AF XY: 0.437 AC XY: 32372 AN XY: 74130

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.425

Alfa AF: 0.501 Hom.: 2515

Bravo AF: 0.418

Asia WGS AF: 0.325 AC: 1133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.025
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2802643; hg19: chr1-215197622;