rs1556905

chr1-215188249-C-Achr1-215188249-C-G

Variant summary

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

The NM_001017425.3(KCNK2):c.824-6704C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,012 control chromosomes in the GnomAD database, including 10,815 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 0.37 (10815 hom., cov: 33)
• Consequence: KCNK2 NM_001017425.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

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 (SAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK2	NM_001017425.3	c.824-6704C>A		intron_variant		ENST00000444842.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK2	ENST00000444842.7	c.824-6704C>A		intron_variant		1	NM_001017425.3

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56163 AN: 151894 Hom.: 10811 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.370 AC: 56184 AN: 152012 Hom.: 10815 Cov.: 33 AF XY: 0.372 AC XY: 27600 AN XY: 74290

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.430

Alfa AF: 0.415 Hom.: 17950

Bravo AF: 0.365

Asia WGS AF: 0.465 AC: 1615 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.015
Dann	Benign	0.29

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: rs1556905; hg19: chr1-215361592;