rs1662987

Variant names:

• chr2-26715314-G-A
• rs1662987
• NM_002246.3:c.284-12353G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-26715314-G-A
• chr2-26715314-G-C
• chr2-26715314-G-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.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
• Publications: 4 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=-0.92).
• 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 rank	MANE	Protein	UniProt
KCNK3	NM_002246.3	c.284-12353G>A		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.284-12353G>A		intron_variant	Intron 1 of 1	1	NM_002246.3	ENSP00000306275.3

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

African (AFR) AF: 0.715 AC: 29665 AN: 41490

American (AMR) AF: 0.767 AC: 11724 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2529 AN: 3472

East Asian (EAS) AF: 0.695 AC: 3591 AN: 5170

South Asian (SAS) AF: 0.782 AC: 3774 AN: 4826

European-Finnish (FIN) AF: 0.738 AC: 7820 AN: 10592

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.759 AC: 51629 AN: 67990

Other (OTH) AF: 0.738 AC: 1561 AN: 2114

Alfa AF: 0.759 Hom.: 79913

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
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: rs1662987; hg19: chr2-26938182;