chr1-196485498-G-A

Variant names:

• chr1-196485498-G-A
• rs1416962
• NM_198503.5:c.276-3119C>T

Variant summary

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

The NM_198503.5(KCNT2):​c.276-3119C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,666 control chromosomes in the GnomAD database, including 19,472 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 0.47 (19472 hom., cov: 31)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• 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, 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.6 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.276-3119C>T		intron	N/A	NP_940905.2
	KCNT2	NM_001287819.3		c.276-3119C>T		intron	N/A	NP_001274748.1
	KCNT2	NM_001287820.3		c.276-3119C>T		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.276-3119C>T		intron	N/A	ENSP00000294725.8
	KCNT2	ENST00000367433.9	TSL:1	c.276-3119C>T		intron	N/A	ENSP00000356403.5
	KCNT2	ENST00000609185.5	TSL:1	c.276-3119C>T		intron	N/A	ENSP00000476657.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71790 AN: 151546 Hom.: 19469 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.473 AC: 71803 AN: 151666 Hom.: 19472 Cov.: 31 AF XY: 0.473 AC XY: 35026 AN XY: 74114

African (AFR) AF: 0.182 AC: 7541 AN: 41376

American (AMR) AF: 0.511 AC: 7766 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2110 AN: 3466

East Asian (EAS) AF: 0.605 AC: 3110 AN: 5138

South Asian (SAS) AF: 0.607 AC: 2918 AN: 4810

European-Finnish (FIN) AF: 0.517 AC: 5449 AN: 10538

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.605 AC: 41030 AN: 67824

Other (OTH) AF: 0.522 AC: 1097 AN: 2102

Alfa AF: 0.497 Hom.: 2906

Bravo AF: 0.462

Asia WGS AF: 0.550 AC: 1913 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.54
DANN	Benign	0.67
PhyloP100		-1.5
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: rs1416962; hg19: chr1-196454628;