chr1-215152892-G-A

Variant names:

• chr1-215152892-G-A
• rs10779646
• NM_001017425.3:c.476-16307G>A

Variant summary

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

The NM_001017425.3(KCNK2):​c.476-16307G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 152,030 control chromosomes in the GnomAD database, including 26,298 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 0.56 (26298 hom., cov: 32)
• Consequence: KCNK2 NM_001017425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK2	NM_001017425.3	c.476-16307G>A		intron_variant	Intron 3 of 6	ENST00000444842.7	NP_001017425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK2	ENST00000444842.7	c.476-16307G>A		intron_variant	Intron 3 of 6	1	NM_001017425.3	ENSP00000394033.2

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85853 AN: 151912 Hom.: 26307 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.565 AC: 85860 AN: 152030 Hom.: 26298 Cov.: 32 AF XY: 0.564 AC XY: 41925 AN XY: 74330

African (AFR) AF: 0.333 AC: 13823 AN: 41474

American (AMR) AF: 0.555 AC: 8466 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2036 AN: 3472

East Asian (EAS) AF: 0.652 AC: 3377 AN: 5176

South Asian (SAS) AF: 0.357 AC: 1723 AN: 4822

European-Finnish (FIN) AF: 0.776 AC: 8208 AN: 10572

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.678 AC: 46090 AN: 67946

Other (OTH) AF: 0.550 AC: 1162 AN: 2114

Alfa AF: 0.617 Hom.: 3643

Bravo AF: 0.547

Asia WGS AF: 0.478 AC: 1666 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.38
PhyloP100		0.10
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: rs10779646; hg19: chr1-215326235; COSMIC: COSV67210215;