chr1-215188864-G-A

Position:

• chr1-215188864-G-A

Variant summary

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

The NM_001017425.3(KCNK2):​c.824-6089G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,046 control chromosomes in the GnomAD database, including 2,879 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 0.17 (2879 hom., cov: 32)
• Consequence: KCNK2 NM_001017425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK2	NM_001017425.3	c.824-6089G>A		intron_variant		ENST00000444842.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK2	ENST00000444842.7	c.824-6089G>A		intron_variant		1	NM_001017425.3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26445 AN: 151928 Hom.: 2877 Cov.: 32

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.174 AC: 26438 AN: 152046 Hom.: 2879 Cov.: 32 AF XY: 0.179 AC XY: 13333 AN XY: 74322

Gnomad4 AFR AF: 0.0477

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.201

Alfa AF: 0.217 Hom.: 3767

Bravo AF: 0.163

Asia WGS AF: 0.335 AC: 1162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.46

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: rs10494994; hg19: chr1-215362207;