1-215216266-T-C

Position:

• chr1-215216266-T-C

Variant summary

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

The NM_001017425.3(KCNK2):​c.964-18562T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,154 control chromosomes in the GnomAD database, including 20,842 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 0.50 (20842 hom., cov: 31)
• Consequence: KCNK2 NM_001017425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK2	NM_001017425.3	c.964-18562T>C		intron_variant		ENST00000444842.7	NP_001017425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK2	ENST00000444842.7	c.964-18562T>C		intron_variant		1	NM_001017425.3	ENSP00000394033.2

Frequencies

GnomAD3 genomes AF: 0.503 AC: 75933 AN: 151070 Hom.: 20836 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.502 AC: 75951 AN: 151154 Hom.: 20842 Cov.: 31 AF XY: 0.505 AC XY: 37281 AN XY: 73830

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.487

Alfa AF: 0.557 Hom.: 8296

Bravo AF: 0.486

Asia WGS AF: 0.492 AC: 1712 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.74

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: rs11583745; hg19: chr1-215389609;