rs6686529

chr1-215236763-G-Cchr1-215236763-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK2	NM_001017425.3	c.*1618G>C		3_prime_UTR_variant	7/7	ENST00000444842.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK2	ENST00000444842.7	c.*1618G>C		3_prime_UTR_variant	7/7	1	NM_001017425.3

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

Gnomad4 FIN exome AF: 0.750

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

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.732

Alfa AF: 0.751 Hom.: 5065

Bravo AF: 0.716

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.0
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6686529; hg19: chr1-215410106;