1-215227100-G-A

Variant names:

• chr1-215227100-G-A
• rs6670661
• NM_001017425.3:c.964-7728G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 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.964-7728G>A		intron	N/A	NP_001017425.2
	KCNK2	NM_001017424.3		c.952-7728G>A		intron	N/A	NP_001017424.1
	KCNK2	NM_014217.4		c.919-7728G>A		intron	N/A	NP_055032.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK2	ENST00000444842.7	TSL:1 MANE Select	c.964-7728G>A		intron	N/A	ENSP00000394033.2
	KCNK2	ENST00000391895.6	TSL:1	c.952-7728G>A		intron	N/A	ENSP00000375765.2
	KCNK2	ENST00000391894.6	TSL:1	c.919-7728G>A		intron	N/A	ENSP00000375764.2

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

African (AFR) AF: 0.316 AC: 13093 AN: 41474

American (AMR) AF: 0.572 AC: 8742 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1747 AN: 3472

East Asian (EAS) AF: 0.613 AC: 3157 AN: 5148

South Asian (SAS) AF: 0.341 AC: 1646 AN: 4824

European-Finnish (FIN) AF: 0.686 AC: 7245 AN: 10566

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40078 AN: 67980

Other (OTH) AF: 0.495 AC: 1047 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.29
DANN	Benign	0.17
PhyloP100		-0.65
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: rs6670661; hg19: chr1-215400443;