2-26709163-C-T

Variant names:

• chr2-26709163-C-T
• rs2586886
• NM_002246.3:c.283+16005C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002246.3(KCNK3):​c.283+16005C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,978 control chromosomes in the GnomAD database, including 25,811 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 0.58 (25811 hom., cov: 31)
• Consequence: KCNK3 NM_002246.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430
• Publications: 16 publications found

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]

KCNK3 Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• pulmonary hypertension, primary, 4

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• heritable pulmonary arterial hypertension

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNK3	NM_002246.3	c.283+16005C>T		intron_variant	Intron 1 of 1	ENST00000302909.4	NP_002237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNK3	ENST00000302909.4	c.283+16005C>T		intron_variant	Intron 1 of 1	1	NM_002246.3	ENSP00000306275.3

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87579 AN: 151860 Hom.: 25761 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.577 AC: 87680 AN: 151978 Hom.: 25811 Cov.: 31 AF XY: 0.573 AC XY: 42552 AN XY: 74276

African (AFR) AF: 0.542 AC: 22463 AN: 41432

American (AMR) AF: 0.688 AC: 10508 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2103 AN: 3470

East Asian (EAS) AF: 0.250 AC: 1295 AN: 5176

South Asian (SAS) AF: 0.541 AC: 2597 AN: 4800

European-Finnish (FIN) AF: 0.531 AC: 5607 AN: 10558

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41044 AN: 67964

Other (OTH) AF: 0.608 AC: 1281 AN: 2106

Alfa AF: 0.582 Hom.: 18649

Bravo AF: 0.588

Asia WGS AF: 0.463 AC: 1611 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.49
PhyloP100		-0.43
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: rs2586886; hg19: chr2-26932031;