1-196382020-A-C

Variant names:

• chr1-196382020-A-C
• rs2027368
• NM_198503.5:c.1295-8772T>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.1295-8772T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,040 control chromosomes in the GnomAD database, including 5,960 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 0.27 (5960 hom., cov: 32)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNT2	NM_198503.5	c.1295-8772T>G		intron_variant	Intron 13 of 27	ENST00000294725.14	NP_940905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNT2	ENST00000294725.14	c.1295-8772T>G		intron_variant	Intron 13 of 27	1	NM_198503.5	ENSP00000294725.8

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41124 AN: 151922 Hom.: 5957 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.271 AC: 41133 AN: 152040 Hom.: 5960 Cov.: 32 AF XY: 0.276 AC XY: 20524 AN XY: 74276

African (AFR) AF: 0.153 AC: 6343 AN: 41526

American (AMR) AF: 0.334 AC: 5102 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1218 AN: 3470

East Asian (EAS) AF: 0.333 AC: 1721 AN: 5166

South Asian (SAS) AF: 0.310 AC: 1492 AN: 4820

European-Finnish (FIN) AF: 0.346 AC: 3634 AN: 10498

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20633 AN: 67964

Other (OTH) AF: 0.275 AC: 581 AN: 2116

Alfa AF: 0.284 Hom.: 8360

Bravo AF: 0.262

Asia WGS AF: 0.316 AC: 1095 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.73
PhyloP100		0.16
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: rs2027368; hg19: chr1-196351150;