chr1-196578558-C-T

Variant names:

• chr1-196578558-C-T
• rs4294368
• NM_198503.5:c.95+29657G>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.95+29657G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,042 control chromosomes in the GnomAD database, including 49,932 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 0.78 (49932 hom., cov: 31)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• Publications: 2 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, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT2	NM_198503.5	MANE Select	c.95+29657G>A		intron	N/A	NP_940905.2
	KCNT2	NM_001287819.3		c.95+29657G>A		intron	N/A	NP_001274748.1	Q6UVM3-2
	KCNT2	NM_001287820.3		c.95+29657G>A		intron	N/A	NP_001274749.1	Q6UVM3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT2	ENST00000294725.14	TSL:1 MANE Select	c.95+29657G>A		intron	N/A	ENSP00000294725.8	Q6UVM3-1
	KCNT2	ENST00000367433.9	TSL:1	c.95+29657G>A		intron	N/A	ENSP00000356403.5	Q6UVM3-2
	KCNT2	ENST00000609185.5	TSL:1	c.95+29657G>A		intron	N/A	ENSP00000476657.1	Q6UVM3-3

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118993 AN: 151924 Hom.: 49919 Cov.: 31

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.974

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.783 AC: 119044 AN: 152042 Hom.: 49932 Cov.: 31 AF XY: 0.787 AC XY: 58472 AN XY: 74324

African (AFR) AF: 0.448 AC: 18537 AN: 41408

American (AMR) AF: 0.898 AC: 13711 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.974 AC: 3383 AN: 3472

East Asian (EAS) AF: 0.966 AC: 4990 AN: 5166

South Asian (SAS) AF: 0.921 AC: 4445 AN: 4828

European-Finnish (FIN) AF: 0.860 AC: 9106 AN: 10588

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61924 AN: 67992

Other (OTH) AF: 0.833 AC: 1759 AN: 2112

Alfa AF: 0.885 Hom.: 62340

Bravo AF: 0.773

Asia WGS AF: 0.893 AC: 3106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.54
PhyloP100		-0.58
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: rs4294368; hg19: chr1-196547688;