1-215218497-C-T

Variant names:

• chr1-215218497-C-T
• rs12143625
• NM_001017425.3:c.964-16331C>T

Variant summary

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

The NM_001017425.3(KCNK2):​c.964-16331C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,076 control chromosomes in the GnomAD database, including 37,400 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 0.69 (37400 hom., cov: 32)
• Consequence: KCNK2 NM_001017425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017425.3. 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_001017425.3	MANE Select	c.964-16331C>T		intron	N/A	NP_001017425.2
	KCNK2	NM_001017424.3		c.952-16331C>T		intron	N/A	NP_001017424.1
	KCNK2	NM_014217.4		c.919-16331C>T		intron	N/A	NP_055032.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK2	ENST00000444842.7	TSL:1 MANE Select	c.964-16331C>T		intron	N/A	ENSP00000394033.2
	KCNK2	ENST00000391895.6	TSL:1	c.952-16331C>T		intron	N/A	ENSP00000375765.2
	KCNK2	ENST00000391894.6	TSL:1	c.919-16331C>T		intron	N/A	ENSP00000375764.2

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104605 AN: 151956 Hom.: 37393 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.688 AC: 104645 AN: 152076 Hom.: 37400 Cov.: 32 AF XY: 0.684 AC XY: 50875 AN XY: 74348

African (AFR) AF: 0.488 AC: 20245 AN: 41458

American (AMR) AF: 0.743 AC: 11359 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2435 AN: 3472

East Asian (EAS) AF: 0.719 AC: 3721 AN: 5174

South Asian (SAS) AF: 0.538 AC: 2590 AN: 4814

European-Finnish (FIN) AF: 0.801 AC: 8468 AN: 10578

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53278 AN: 67982

Other (OTH) AF: 0.705 AC: 1490 AN: 2112

Alfa AF: 0.744 Hom.: 51955

Bravo AF: 0.678

Asia WGS AF: 0.615 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.68
DANN	Benign	0.63
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12143625; hg19: chr1-215391840;