1-196549893-T-C

Variant names:

• chr1-196549893-T-C
• rs10754192
• NM_198503.5:c.96-57552A>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.96-57552A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 151,740 control chromosomes in the GnomAD database, including 49,485 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 (49485 hom., cov: 31)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 0 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNT2	NM_198503.5	c.96-57552A>G		intron_variant	Intron 1 of 27	ENST00000294725.14	NP_940905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNT2	ENST00000294725.14	c.96-57552A>G		intron_variant	Intron 1 of 27	1	NM_198503.5	ENSP00000294725.8

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118052 AN: 151620 Hom.: 49470 Cov.: 31

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.974

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.778 AC: 118101 AN: 151740 Hom.: 49485 Cov.: 31 AF XY: 0.782 AC XY: 58016 AN XY: 74168

African (AFR) AF: 0.433 AC: 17907 AN: 41368

American (AMR) AF: 0.894 AC: 13593 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.974 AC: 3375 AN: 3464

East Asian (EAS) AF: 0.966 AC: 4954 AN: 5126

South Asian (SAS) AF: 0.921 AC: 4440 AN: 4822

European-Finnish (FIN) AF: 0.859 AC: 9091 AN: 10582

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

European-Non Finnish (NFE) AF: 0.911 AC: 61810 AN: 67872

Other (OTH) AF: 0.829 AC: 1742 AN: 2102

Alfa AF: 0.878 Hom.: 244041

Bravo AF: 0.767

Asia WGS AF: 0.894 AC: 3109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.25
PhyloP100		-0.14
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: rs10754192; hg19: chr1-196519023;