rs7529369

Variant names:

• chr1-196239760-C-T
• rs7529369
• NM_198503.5:c.3212-3690G>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.3212-3690G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 151,908 control chromosomes in the GnomAD database, including 1,232 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 0.10 (1232 hom., cov: 32)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 2 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, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198503.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT2	NM_198503.5	MANE Select	c.3212-3690G>A		intron	N/A	NP_940905.2
	KCNT2	NM_001287819.3		c.3140-3690G>A		intron	N/A	NP_001274748.1	Q6UVM3-2
	KCNT2	NM_001287820.3		c.3011-3690G>A		intron	N/A	NP_001274749.1	Q6UVM3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT2	ENST00000294725.14	TSL:1 MANE Select	c.3212-3690G>A		intron	N/A	ENSP00000294725.8	Q6UVM3-1
	KCNT2	ENST00000367433.9	TSL:1	c.3140-3690G>A		intron	N/A	ENSP00000356403.5	Q6UVM3-2
	KCNT2	ENST00000609185.5	TSL:1	c.3011-3690G>A		intron	N/A	ENSP00000476657.1	Q6UVM3-3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15924 AN: 151788 Hom.: 1231 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.0381

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0388

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0706

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.105 AC: 15938 AN: 151908 Hom.: 1232 Cov.: 32 AF XY: 0.100 AC XY: 7437 AN XY: 74278

African (AFR) AF: 0.221 AC: 9145 AN: 41436

American (AMR) AF: 0.0682 AC: 1038 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0381 AC: 132 AN: 3464

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0393 AC: 189 AN: 4810

European-Finnish (FIN) AF: 0.0372 AC: 394 AN: 10582

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0706 AC: 4792 AN: 67906

Other (OTH) AF: 0.103 AC: 216 AN: 2106

Alfa AF: 0.0773 Hom.: 280

Bravo AF: 0.112

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.16
PhyloP100		0.063
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: rs7529369; hg19: chr1-196208890;