chr2-26715314-G-A

Position:

• chr2-26715314-G-A

Variant summary

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

The NM_002246.3(KCNK3):​c.284-12353G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,146 control chromosomes in the GnomAD database, including 42,337 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 0.74 (42337 hom., cov: 34)
• Consequence: KCNK3 NM_002246.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648

Genes affected

KCNK3 (HGNC:6278): (potassium two pore domain channel subfamily K member 3) This gene encodes a member of the superfamily of potassium channel proteins that contain two pore-forming P domains. The encoded protein is an outwardly rectifying channel that is sensitive to changes in extracellular pH and is inhibited by extracellular acidification. Also referred to as an acid-sensitive potassium channel, it is activated by the anesthetics halothane and isoflurane. Although three transcripts are detected in northern blots, there is currently no sequence available to confirm transcript variants for this gene. [provided by RefSeq, Aug 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 = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNK3	NM_002246.3	c.284-12353G>A		intron_variant		ENST00000302909.4	NP_002237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNK3	ENST00000302909.4	c.284-12353G>A		intron_variant		1	NM_002246.3	ENSP00000306275	P1

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113113 AN: 152028 Hom.: 42282 Cov.: 34

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.744 AC: 113229 AN: 152146 Hom.: 42337 Cov.: 34 AF XY: 0.744 AC XY: 55325 AN XY: 74384

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.759

Gnomad4 OTH AF: 0.738

Alfa AF: 0.763 Hom.: 57558

Bravo AF: 0.744

Asia WGS AF: 0.773 AC: 2688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.081
DANN	Benign	0.57

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: rs1662987; hg19: chr2-26938182;