1-215236763-G-C

Variant names:

• chr1-215236763-G-C
• rs6686529
• NM_001017425.3:c.*1618G>C

Variant summary

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

The NM_001017425.3(KCNK2):​c.*1618G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 151,778 control chromosomes in the GnomAD database, including 40,256 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 0.72 (40255 hom., cov: 30)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: KCNK2 NM_001017425.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017425.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK2	NM_001017425.3	MANE Select	c.*1618G>C		3_prime_UTR	Exon 7 of 7	NP_001017425.2
	KCNK2	NM_001017424.3		c.*1618G>C		3_prime_UTR	Exon 7 of 7	NP_001017424.1
	KCNK2	NM_014217.4		c.*1618G>C		3_prime_UTR	Exon 7 of 7	NP_055032.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK2	ENST00000444842.7	TSL:1 MANE Select	c.*1618G>C		3_prime_UTR	Exon 7 of 7	ENSP00000394033.2

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109737 AN: 151658 Hom.: 40232 Cov.: 30

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.731

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.724 AC: 109810 AN: 151774 Hom.: 40255 Cov.: 30 AF XY: 0.718 AC XY: 53240 AN XY: 74158

African (AFR) AF: 0.616 AC: 25499 AN: 41388

American (AMR) AF: 0.746 AC: 11361 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2459 AN: 3470

East Asian (EAS) AF: 0.671 AC: 3466 AN: 5168

South Asian (SAS) AF: 0.531 AC: 2552 AN: 4804

European-Finnish (FIN) AF: 0.796 AC: 8345 AN: 10484

Middle Eastern (MID) AF: 0.707 AC: 205 AN: 290

European-Non Finnish (NFE) AF: 0.788 AC: 53525 AN: 67912

Other (OTH) AF: 0.732 AC: 1547 AN: 2112

Alfa AF: 0.751 Hom.: 5065

Bravo AF: 0.716

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.59
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6686529; hg19: chr1-215410106;