1-196416519-T-C

Variant names:

• chr1-196416519-T-C
• rs3927686
• NM_198503.5:c.1185+6531A>G

Variant summary

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

The NM_198503.5(KCNT2):​c.1185+6531A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 151,806 control chromosomes in the GnomAD database, including 37,066 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 0.70 (37066 hom., cov: 30)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 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.1185+6531A>G		intron	N/A	NP_940905.2
	KCNT2	NM_001287819.3		c.1185+6531A>G		intron	N/A	NP_001274748.1	Q6UVM3-2
	KCNT2	NM_001287820.3		c.1185+6531A>G		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.1185+6531A>G		intron	N/A	ENSP00000294725.8	Q6UVM3-1
	KCNT2	ENST00000367433.9	TSL:1	c.1185+6531A>G		intron	N/A	ENSP00000356403.5	Q6UVM3-2
	KCNT2	ENST00000609185.5	TSL:1	c.1185+6531A>G		intron	N/A	ENSP00000476657.1	Q6UVM3-3

Frequencies

GnomAD3 genomes AF: 0.698 AC: 105868 AN: 151688 Hom.: 37027 Cov.: 30

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.698 AC: 105962 AN: 151806 Hom.: 37066 Cov.: 30 AF XY: 0.693 AC XY: 51380 AN XY: 74138

African (AFR) AF: 0.735 AC: 30468 AN: 41432

American (AMR) AF: 0.654 AC: 9945 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2253 AN: 3466

East Asian (EAS) AF: 0.663 AC: 3393 AN: 5116

South Asian (SAS) AF: 0.689 AC: 3315 AN: 4810

European-Finnish (FIN) AF: 0.655 AC: 6916 AN: 10566

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47385 AN: 67896

Other (OTH) AF: 0.709 AC: 1493 AN: 2106

Alfa AF: 0.700 Hom.: 49857

Bravo AF: 0.702

Asia WGS AF: 0.675 AC: 2348 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.7
DANN	Benign	0.75
PhyloP100		0.073
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: rs3927686; hg19: chr1-196385649; COSMIC: COSV54070780;