1-215077884-G-A

Variant names:

• chr1-215077884-G-A
• rs12136349
• ENST00000391895.6:c.35-8484G>A

Variant summary

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

The ENST00000391895.6(KCNK2):​c.35-8484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,770 control chromosomes in the GnomAD database, including 9,525 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 0.32 (9525 hom., cov: 32)
• Consequence: KCNK2 ENST00000391895.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.596
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000391895.6. 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_001017424.3		c.35-8484G>A		intron	N/A	NP_001017424.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK2	ENST00000391895.6	TSL:1	c.35-8484G>A		intron	N/A	ENSP00000375765.2
	KCNK2	ENST00000467031.5	TSL:1	n.35-8484G>A		intron	N/A	ENSP00000420203.1
	KCNK2	ENST00000486921.5	TSL:5	n.35-8484G>A		intron	N/A	ENSP00000418706.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48661 AN: 151652 Hom.: 9490 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0949

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.321 AC: 48752 AN: 151770 Hom.: 9525 Cov.: 32 AF XY: 0.315 AC XY: 23387 AN XY: 74138

African (AFR) AF: 0.549 AC: 22720 AN: 41380

American (AMR) AF: 0.237 AC: 3615 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3468

East Asian (EAS) AF: 0.0945 AC: 486 AN: 5142

South Asian (SAS) AF: 0.257 AC: 1236 AN: 4810

European-Finnish (FIN) AF: 0.199 AC: 2085 AN: 10474

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16659 AN: 67954

Other (OTH) AF: 0.343 AC: 720 AN: 2102

Alfa AF: 0.278 Hom.: 8574

Bravo AF: 0.332

Asia WGS AF: 0.215 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.73
PhyloP100		-0.60
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: rs12136349; hg19: chr1-215251227;