1-196273929-C-T

Variant names:

• chr1-196273929-C-T
• rs2245414
• NM_198503.5:c.2910+6931G>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.2910+6931G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 151,484 control chromosomes in the GnomAD database, including 40,214 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 0.69 (40214 hom., cov: 32)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 1 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 (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNT2	NM_198503.5	c.2910+6931G>A		intron_variant	Intron 25 of 27	ENST00000294725.14	NP_940905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNT2	ENST00000294725.14	c.2910+6931G>A		intron_variant	Intron 25 of 27	1	NM_198503.5	ENSP00000294725.8

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104247 AN: 151366 Hom.: 40207 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.827

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.688 AC: 104273 AN: 151484 Hom.: 40214 Cov.: 32 AF XY: 0.695 AC XY: 51431 AN XY: 74016

African (AFR) AF: 0.306 AC: 12668 AN: 41374

American (AMR) AF: 0.786 AC: 11924 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3089 AN: 3466

East Asian (EAS) AF: 0.945 AC: 4882 AN: 5164

South Asian (SAS) AF: 0.854 AC: 4125 AN: 4828

European-Finnish (FIN) AF: 0.830 AC: 8775 AN: 10578

Middle Eastern (MID) AF: 0.822 AC: 240 AN: 292

European-Non Finnish (NFE) AF: 0.831 AC: 56197 AN: 67612

Other (OTH) AF: 0.717 AC: 1502 AN: 2096

Alfa AF: 0.740 Hom.: 5288

Bravo AF: 0.669

Asia WGS AF: 0.832 AC: 2873 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.49
PhyloP100		0.20
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: rs2245414; hg19: chr1-196243059;