rs6667764

Positions:

• chr1-215107880-C-G

Variant summary

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

The NM_001017425.3(KCNK2):​c.358-16753C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,972 control chromosomes in the GnomAD database, including 26,517 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 0.57 (26517 hom., cov: 32)
• Consequence: KCNK2 NM_001017425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK2	NM_001017425.3	c.358-16753C>G		intron_variant		ENST00000444842.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK2	ENST00000444842.7	c.358-16753C>G		intron_variant		1	NM_001017425.3

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86465 AN: 151852 Hom.: 26525 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.569 AC: 86478 AN: 151972 Hom.: 26517 Cov.: 32 AF XY: 0.569 AC XY: 42235 AN XY: 74258

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.551

Alfa AF: 0.626 Hom.: 3860

Bravo AF: 0.554

Asia WGS AF: 0.500 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.52

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: rs6667764; hg19: chr1-215281223;