1-215024279-A-C

Variant names:

• chr1-215024279-A-C
• rs2802643
• ENST00000391895.6:c.34+18324A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.92).
• 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 rank	MANE	Protein	UniProt
KCNK2	NM_001017424.3	c.34+18324A>C		intron_variant	Intron 1 of 6		NP_001017424.1
KCNK2	XM_017001249.2	c.-84-11988A>C		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+18324A>C		intron_variant	Intron 1 of 6	1		ENSP00000375765.2
KCNK2	ENST00000467031.5	n.34+18324A>C		intron_variant	Intron 1 of 5	1		ENSP00000420203.1
KCNK2	ENST00000486921.5	n.34+18324A>C		intron_variant	Intron 1 of 6	5		ENSP00000418706.1

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

African (AFR) AF: 0.233 AC: 9658 AN: 41464

American (AMR) AF: 0.420 AC: 6411 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1858 AN: 3464

East Asian (EAS) AF: 0.471 AC: 2420 AN: 5140

South Asian (SAS) AF: 0.212 AC: 1021 AN: 4826

European-Finnish (FIN) AF: 0.652 AC: 6831 AN: 10482

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 36952 AN: 67798

Other (OTH) AF: 0.425 AC: 898 AN: 2112

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
PhyloP100		-4.6
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: rs2802643; hg19: chr1-215197622;