rs1769996

Variant names:

• chr1-196383911-C-T
• rs1769996
• NM_198503.5:c.1295-10663G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198503.5(KCNT2):​c.1295-10663G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,912 control chromosomes in the GnomAD database, including 31,828 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 0.64 (31828 hom., cov: 31)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 57

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198503.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT2	NM_198503.5	MANE Select	c.1295-10663G>A		intron	N/A	NP_940905.2
	KCNT2	NM_001287819.3		c.1295-10663G>A		intron	N/A	NP_001274748.1
	KCNT2	NM_001287820.3		c.1295-10663G>A		intron	N/A	NP_001274749.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT2	ENST00000294725.14	TSL:1 MANE Select	c.1295-10663G>A		intron	N/A	ENSP00000294725.8
	KCNT2	ENST00000367433.9	TSL:1	c.1295-10663G>A		intron	N/A	ENSP00000356403.5
	KCNT2	ENST00000609185.5	TSL:1	c.1295-10663G>A		intron	N/A	ENSP00000476657.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97774 AN: 151794 Hom.: 31795 Cov.: 31

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.644 AC: 97859 AN: 151912 Hom.: 31828 Cov.: 31 AF XY: 0.642 AC XY: 47688 AN XY: 74242

African (AFR) AF: 0.553 AC: 22908 AN: 41416

American (AMR) AF: 0.630 AC: 9617 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2251 AN: 3466

East Asian (EAS) AF: 0.666 AC: 3430 AN: 5150

South Asian (SAS) AF: 0.689 AC: 3323 AN: 4824

European-Finnish (FIN) AF: 0.654 AC: 6896 AN: 10538

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47238 AN: 67938

Other (OTH) AF: 0.665 AC: 1404 AN: 2112

Alfa AF: 0.673 Hom.: 4323

Bravo AF: 0.641

Asia WGS AF: 0.662 AC: 2302 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.070
DANN	Benign	0.39
PhyloP100		-1.0
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: rs1769996; hg19: chr1-196353041; COSMIC: COSV54070718;