rs1663002

chr2-26728581-G-Achr2-26728581-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002246.3(KCNK3):c.*13G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,421,272 control chromosomes in the GnomAD database, including 702,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71665 hom., cov: 32)
  • Exomes 𝑓: 1.0 (631086 hom.)
• Consequence: KCNK3 NM_002246.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.46

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 2-26728581-G-A is Benign according to our data. Variant chr2-26728581-G-A is described in ClinVar as [Benign]. Clinvar id is 402999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-26728581-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK3	NM_002246.3	c.*13G>A		3_prime_UTR_variant	2/2	ENST00000302909.4
KCNK3	XM_005264293.3	c.*13G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK3	ENST00000302909.4	c.*13G>A		3_prime_UTR_variant	2/2	1	NM_002246.3	P1

Frequencies

GnomAD3 genomes AF: 0.969 AC: 147425 AN: 152122 Hom.: 71603 Cov.: 32

Gnomad AFR AF: 0.895

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.984

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.972

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.977

GnomAD3 exomes AF: 0.993 AC: 63315 AN: 63758 Hom.: 31461 AF XY: 0.995 AC XY: 32931 AN XY: 33100

Gnomad AFR exome AF: 0.891

Gnomad AMR exome AF: 0.993

Gnomad ASJ exome AF: 0.998

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.997 AC: 1265449 AN: 1269032 Hom.: 631086 Cov.: 44 AF XY: 0.998 AC XY: 612914 AN XY: 614450

Gnomad4 AFR exome AF: 0.891

Gnomad4 AMR exome AF: 0.991

Gnomad4 ASJ exome AF: 0.999

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.992

GnomAD4 genome AF: 0.969 AC: 147546 AN: 152240 Hom.: 71665 Cov.: 32 AF XY: 0.970 AC XY: 72197 AN XY: 74422

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.984

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.977

Alfa AF: 0.982 Hom.: 9114

Bravo AF: 0.965

Asia WGS AF: 0.997 AC: 3466 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Pulmonary hypertension, primary, 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	15
Dann	Benign	0.88

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: rs1663002; hg19: chr2-26951449;