rs12136349

Positions:

• chr1-215077884-G-A
• chr1-215077884-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK2	NM_001017424.3	c.35-8484G>A		intron_variant			NP_001017424.1
KCNK2	XM_017001249.2	c.5-8484G>A		intron_variant			XP_016856738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK2	ENST00000391895.6	c.35-8484G>A		intron_variant		1		ENSP00000375765
KCNK2	ENST00000467031.5	c.35-8484G>A		intron_variant, NMD_transcript_variant		1		ENSP00000420203
KCNK2	ENST00000486921.5	c.35-8484G>A		intron_variant, NMD_transcript_variant		5		ENSP00000418706

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

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.0945

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.343

Alfa AF: 0.269 Hom.: 6085

Bravo AF: 0.332

Asia WGS AF: 0.215 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12136349; hg19: chr1-215251227;