NM_001017425.3:c.358-16753C>G

Variant names:

• chr1-215107880-C-G
• rs6667764
• NM_001017425.3:c.358-16753C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.89).
• 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 rank	MANE	Protein	UniProt
KCNK2	NM_001017425.3	c.358-16753C>G		intron_variant	Intron 2 of 6	ENST00000444842.7	NP_001017425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK2	ENST00000444842.7	c.358-16753C>G		intron_variant	Intron 2 of 6	1	NM_001017425.3	ENSP00000394033.2

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

African (AFR) AF: 0.344 AC: 14268 AN: 41434

American (AMR) AF: 0.561 AC: 8555 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2032 AN: 3466

East Asian (EAS) AF: 0.650 AC: 3343 AN: 5142

South Asian (SAS) AF: 0.372 AC: 1796 AN: 4822

European-Finnish (FIN) AF: 0.777 AC: 8211 AN: 10574

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46129 AN: 67952

Other (OTH) AF: 0.551 AC: 1165 AN: 2114

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
PhyloP100		0.23
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: rs6667764; hg19: chr1-215281223;