rs12567520

chr1-215155924-G-Achr1-215155924-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017425.3(KCNK2):c.476-13275G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,040 control chromosomes in the GnomAD database, including 2,089 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 0.14 (2089 hom., cov: 32)
• Consequence: KCNK2 NM_001017425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK2	NM_001017425.3	c.476-13275G>A		intron_variant		ENST00000444842.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK2	ENST00000444842.7	c.476-13275G>A		intron_variant		1	NM_001017425.3

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21398 AN: 151922 Hom.: 2083 Cov.: 32

Gnomad AFR AF: 0.0357

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.141 AC: 21408 AN: 152040 Hom.: 2089 Cov.: 32 AF XY: 0.147 AC XY: 10901 AN XY: 74316

Gnomad4 AFR AF: 0.0356

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.170

Alfa AF: 0.162 Hom.: 1139

Bravo AF: 0.138

Asia WGS AF: 0.363 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.6
Dann	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs12567520; hg19: chr1-215329267;