1-215017904-G-T

Variant names:

• chr1-215017904-G-T
• rs2841608
• ENST00000391895.6:c.34+11949G>T

Variant summary

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

The ENST00000391895.6(KCNK2):​c.34+11949G>T 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 151,928 control chromosomes in the GnomAD database, including 25,515 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 (25515 hom., cov: 32)
• Consequence: KCNK2 ENST00000391895.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.762 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.34+11949G>T		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.34+11949G>T		intron	N/A	ENSP00000375765.2
	KCNK2	ENST00000467031.5	TSL:1	n.34+11949G>T		intron	N/A	ENSP00000420203.1
	KCNK2	ENST00000486921.5	TSL:5	n.34+11949G>T		intron	N/A	ENSP00000418706.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85003 AN: 151810 Hom.: 25474 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.454

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: 85103 AN: 151928 Hom.: 25515 Cov.: 32 AF XY: 0.561 AC XY: 41670 AN XY: 74220

African (AFR) AF: 0.766 AC: 31780 AN: 41476

American (AMR) AF: 0.579 AC: 8837 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1599 AN: 3460

East Asian (EAS) AF: 0.527 AC: 2716 AN: 5152

South Asian (SAS) AF: 0.783 AC: 3772 AN: 4818

European-Finnish (FIN) AF: 0.345 AC: 3638 AN: 10530

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30799 AN: 67914

Other (OTH) AF: 0.574 AC: 1211 AN: 2110

Alfa AF: 0.298 Hom.: 589

Bravo AF: 0.581

Asia WGS AF: 0.671 AC: 2326 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.55
DANN	Benign	0.27
PhyloP100		-0.26
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: rs2841608; hg19: chr1-215191247;