1-215218497-C-T

Position:

• chr1-215218497-C-T

Variant summary

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

The ENST00000444842.7(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 ENST00000444842.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK2	NM_001017425.3	c.964-16331C>T		intron_variant		ENST00000444842.7	NP_001017425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK2	ENST00000444842.7	c.964-16331C>T		intron_variant		1	NM_001017425.3	ENSP00000394033

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

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.705

Alfa AF: 0.754 Hom.: 39910

Bravo AF: 0.678

Asia WGS AF: 0.615 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.68
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: rs12143625; hg19: chr1-215391840;