2-18208358-A-G

Position:

• chr2-18208358-A-G

Variant summary

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

The ENST00000465292.5(KCNS3):​n.424+37850A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,178 control chromosomes in the GnomAD database, including 61,709 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 0.90 (61709 hom., cov: 33)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387

Genes affected

KCNS3 (HGNC:6302): (potassium voltage-gated channel modifier subfamily S member 3) Voltage-gated potassium channels form the largest and most diversified class of ion channels and are present in both excitable and nonexcitable cells. Their main functions are associated with the regulation of the resting membrane potential and the control of the shape and frequency of action potentials. The alpha subunits are of 2 types: those that are functional by themselves and those that are electrically silent but capable of modulating the activity of specific functional alpha subunits. The protein encoded by this gene is not functional by itself but can form heteromultimers with member 1 and with member 2 (and possibly other members) of the Shab-related subfamily of potassium voltage-gated channel proteins. This gene belongs to the S subfamily of the potassium channel family. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNS3	ENST00000465292.5	n.424+37850A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136531 AN: 152060 Hom.: 61687 Cov.: 33

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.912

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

GnomAD4 genome AF: 0.898 AC: 136606 AN: 152178 Hom.: 61709 Cov.: 33 AF XY: 0.898 AC XY: 66781 AN XY: 74396

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.956

Gnomad4 EAS AF: 0.882

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.945

Gnomad4 NFE AF: 0.949

Gnomad4 OTH AF: 0.913

Alfa AF: 0.934 Hom.: 30073

Bravo AF: 0.891

Asia WGS AF: 0.879 AC: 3046 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2345516; hg19: chr2-18389624;