Genetic Variant KCNT2:c.1404-155C>T (chr1-196342383-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198503.5(KCNT2):c.1404-155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 378,002 control chromosomes in the GnomAD database, including 46,705 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 0.42 ( 14734 hom., cov: 26)

Exomes 𝑓: 0.51 ( 31971 hom. )

Consequence

KCNT2
NM_198503.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.201

Publications

2 publications found

Variant links:

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)

KCNT2 links:

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ACMG classification

Classification was made for transcript

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 = 0.679 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KCNT2	NM_198503.5	MANE Select	c.1404-155C>T	intron	N/A	NP_940905.2
KCNT2	NM_001287819.3		c.1404-155C>T	intron	N/A	NP_001274748.1
KCNT2	NM_001287820.3		c.1404-1813C>T	intron	N/A	NP_001274749.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KCNT2	ENST00000294725.14	TSL:1 MANE Select	c.1404-155C>T	intron	N/A	ENSP00000294725.8
KCNT2	ENST00000367433.9	TSL:1	c.1404-155C>T	intron	N/A	ENSP00000356403.5
KCNT2	ENST00000609185.5	TSL:1	c.1404-1813C>T	intron	N/A	ENSP00000476657.1

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

60513

AN:

145420

Hom.:

14748

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.584

Gnomad EAS

AF:

0.699

Gnomad SAS

AF:

0.595

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.453

GnomAD4 exome

AF:

0.514

AC:

119614

AN:

232522

Hom.:

31971

AF XY:

0.516

AC XY:

61944

AN XY:

120138

show subpopulations

African (AFR)

AF:

0.130

AC:

816

AN:

6268

American (AMR)

AF:

0.442

AC:

2802

AN:

6340

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

4320

AN:

7454

East Asian (EAS)

AF:

0.715

AC:

13511

AN:

18896

South Asian (SAS)

AF:

0.574

AC:

3060

AN:

5334

European-Finnish (FIN)

AF:

0.465

AC:

8390

AN:

18042

Middle Eastern (MID)

AF:

0.630

AC:

1615

AN:

2562

European-Non Finnish (NFE)

AF:

0.508

AC:

77888

AN:

153236

Other (OTH)

AF:

0.501

AC:

7212

AN:

14390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2637

5273

7910

10546

13183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

646

1292

1938

2584

3230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.416

AC:

60479

AN:

145480

Hom.:

14734

Cov.:

AF XY:

0.419

AC XY:

29710

AN XY:

70832

show subpopulations

African (AFR)

AF:

0.141

AC:

5405

AN:

38402

American (AMR)

AF:

0.453

AC:

6586

AN:

14550

Ashkenazi Jewish (ASJ)

AF:

0.584

AC:

2014

AN:

3450

East Asian (EAS)

AF:

0.698

AC:

3506

AN:

5022

South Asian (SAS)

AF:

0.595

AC:

2796

AN:

4698

European-Finnish (FIN)

AF:

0.475

AC:

4278

AN:

9014

Middle Eastern (MID)

AF:

0.586

AC:

163

AN:

278

European-Non Finnish (NFE)

AF:

0.512

AC:

34356

AN:

67140

Other (OTH)

AF:

0.452

AC:

913

AN:

2022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

1451

2902

4352

5803

7254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.420

Hom.:

2018

Bravo

AF:

0.396

Asia WGS

AF:

0.574

AC:

1993

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.6

(source)

DANN

Benign

0.32

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over