chr1-196607234-C-G

Variant names:

• chr1-196607234-C-G
• rs1360143
• NM_198503.5:c.95+981G>C

Variant summary

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

The NM_198503.5(KCNT2):​c.95+981G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,148 control chromosomes in the GnomAD database, including 49,461 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 (49461 hom., cov: 33)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119
• 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNT2	NM_198503.5	c.95+981G>C		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.95+981G>C		intron_variant	Intron 1 of 27	1	NM_198503.5	ENSP00000294725.8

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118206 AN: 152030 Hom.: 49450 Cov.: 33

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: 0.921

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.777 AC: 118253 AN: 152148 Hom.: 49461 Cov.: 33 AF XY: 0.781 AC XY: 58126 AN XY: 74394

African (AFR) AF: 0.433 AC: 17957 AN: 41442

American (AMR) AF: 0.894 AC: 13675 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.974 AC: 3383 AN: 3472

East Asian (EAS) AF: 0.966 AC: 5001 AN: 5178

South Asian (SAS) AF: 0.921 AC: 4448 AN: 4830

European-Finnish (FIN) AF: 0.859 AC: 9109 AN: 10604

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

European-Non Finnish (NFE) AF: 0.908 AC: 61750 AN: 68004

Other (OTH) AF: 0.825 AC: 1741 AN: 2110

Alfa AF: 0.760 Hom.: 2671

Bravo AF: 0.766

Asia WGS AF: 0.892 AC: 3101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		0.12
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: rs1360143; hg19: chr1-196576364;