rs1416962

Positions:

• chr1-196485498-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198503.5(KCNT2):​c.276-3119C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,666 control chromosomes in the GnomAD database, including 19,472 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 0.47 (19472 hom., cov: 31)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNT2	NM_198503.5	c.276-3119C>T		intron_variant		ENST00000294725.14	NP_940905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNT2	ENST00000294725.14	c.276-3119C>T		intron_variant		1	NM_198503.5	ENSP00000294725.8

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71790 AN: 151546 Hom.: 19469 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.473 AC: 71803 AN: 151666 Hom.: 19472 Cov.: 31 AF XY: 0.473 AC XY: 35026 AN XY: 74114

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.522

Alfa AF: 0.509 Hom.: 2890

Bravo AF: 0.462

Asia WGS AF: 0.550 AC: 1913 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.54
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs1416962; hg19: chr1-196454628;