rs6670661

Positions:

• chr1-215227100-G-A
• chr1-215227100-G-C

Variant summary

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

The NM_001017425.3(KCNK2):​c.964-7728G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 152,072 control chromosomes in the GnomAD database, including 21,141 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 0.51 (21141 hom., cov: 32)
• Consequence: KCNK2 NM_001017425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK2	NM_001017425.3	c.964-7728G>A		intron_variant		ENST00000444842.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK2	ENST00000444842.7	c.964-7728G>A		intron_variant		1	NM_001017425.3

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77464 AN: 151954 Hom.: 21135 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.510 AC: 77498 AN: 152072 Hom.: 21141 Cov.: 32 AF XY: 0.510 AC XY: 37953 AN XY: 74346

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.495

Alfa AF: 0.541 Hom.: 2770

Bravo AF: 0.495

Asia WGS AF: 0.452 AC: 1575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.29
DANN	Benign	0.17

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: rs6670661; hg19: chr1-215400443;