rs1060499537
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_198503.5(KCNT2):c.720T>A(p.Phe240Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
KCNT2
NM_198503.5 missense
NM_198503.5 missense
Scores
4
8
7
Clinical Significance
Conservation
PhyloP100: 3.63
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-196429676-A-T is Pathogenic according to our data. Variant chr1-196429676-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 236299.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNT2 | NM_198503.5 | c.720T>A | p.Phe240Leu | missense_variant | 9/28 | ENST00000294725.14 | NP_940905.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNT2 | ENST00000294725.14 | c.720T>A | p.Phe240Leu | missense_variant | 9/28 | 1 | NM_198503.5 | ENSP00000294725.8 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 57 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 04, 2020 | - - |
KCNT2-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Sydney Children's Hospital, SCHN | Jun 15, 2016 | The affected residue is highly conserved to C.elegans and predicted to be pathogenic using Polyphen, SIFT and CADD (CADD score 25.5, v1.3). It is not present in the ExAC database (accessed July June 2016). At the structural level, the residue Phe-240 has been demonstrated as critical to normal Slick channel gating. The clinical condition is similar to that caused by pathogenic variants in an equivalent functional domain in the related gene KCNT1. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
.;.;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;.;D
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Uncertain
D;D;D
Polyphen
P;B;P
Vest4
MutPred
Loss of catalytic residue at F240 (P = 0.0357);Loss of catalytic residue at F240 (P = 0.0357);Loss of catalytic residue at F240 (P = 0.0357);
MVP
MPC
2.2
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at