dbSNP rs6658788: 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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNT2	NM_198503.5 link	c.1404-155C>T		intron_variant	Intron 14 of 27	ENST00000294725.14	NP_940905.2	Q6UVM3-1A9LNM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNT2	ENST00000294725.14 link	c.1404-155C>T		intron_variant	Intron 14 of 27	1	NM_198503.5	ENSP00000294725.8		Q6UVM3-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over