rs12407399

Positions:

• chr1-196322847-T-C

Variant summary

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

The NM_198503.5(KCNT2):​c.2277-3292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 151,884 control chromosomes in the GnomAD database, including 1,234 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 0.11 (1234 hom., cov: 32)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

Genes affected

KCNT2 (HGNC:18866): (potassium sodium-activated channel subfamily T member 2) Enables chloride-activated potassium channel activity. Involved in potassium ion export across plasma membrane. Located in plasma membrane. Implicated in developmental and epileptic encephalopathy 57. [provided by Alliance of Genome Resources, Apr 2022]

KCNT2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNT2	NM_198503.5	c.2277-3292A>G		intron_variant		ENST00000294725.14	NP_940905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNT2	ENST00000294725.14	c.2277-3292A>G		intron_variant		1	NM_198503.5	ENSP00000294725.8

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16203 AN: 151766 Hom.: 1233 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0476

Gnomad FIN AF: 0.0462

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.107 AC: 16216 AN: 151884 Hom.: 1234 Cov.: 32 AF XY: 0.102 AC XY: 7585 AN XY: 74252

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.0695

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0481

Gnomad4 FIN AF: 0.0462

Gnomad4 NFE AF: 0.0741

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0813 Hom.: 273

Bravo AF: 0.113

Asia WGS AF: 0.0350 AC: 122 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.7
DANN	Benign	0.79

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: rs12407399; hg19: chr1-196291977;