rs10494744

chr1-196573437-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.95+34778A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,150 control chromosomes in the GnomAD database, including 1,046 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 0.10 (1046 hom., cov: 32)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

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]

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 (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNT2	NM_198503.5	c.95+34778A>G		intron_variant		ENST00000294725.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNT2	ENST00000294725.14	c.95+34778A>G		intron_variant		1	NM_198503.5	P4

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15244 AN: 152032 Hom.: 1045 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.0932

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.0851

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

GnomAD4 genome AF: 0.100 AC: 15245 AN: 152150 Hom.: 1046 Cov.: 32 AF XY: 0.0995 AC XY: 7399 AN XY: 74386

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.0931

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.00540

Gnomad4 SAS AF: 0.0653

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.0847

Alfa AF: 0.131 Hom.: 1820

Bravo AF: 0.0888

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.3
Dann	Benign	0.87

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: rs10494744; hg19: chr1-196542567; COSMIC: COSV54071086;