rs1553564139
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001040142.2(SCN2A):c.1A>T(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SCN2A
NM_001040142.2 start_lost
NM_001040142.2 start_lost
Scores
11
3
1
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
SCN2A (HGNC:10588): (sodium voltage-gated channel alpha subunit 2) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with four repeat domains, each of which is composed of six membrane-spanning segments, and one or more regulatory beta subunits. Voltage-gated sodium channels function in the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. Allelic variants of this gene are associated with seizure disorders and autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-165295824-A-T is Pathogenic according to our data. Variant chr2-165295824-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 559888.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN2A | NM_001040142.2 | c.1A>T | p.Met1? | start_lost | 2/27 | ENST00000375437.7 | |
SCN2A | NM_001371246.1 | c.1A>T | p.Met1? | start_lost | 2/27 | ENST00000631182.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.1A>T | p.Met1? | start_lost | 2/27 | 5 | NM_001040142.2 | P1 | |
SCN2A | ENST00000631182.3 | c.1A>T | p.Met1? | start_lost | 2/27 | 5 | NM_001371246.1 |
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: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 11 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Feb 07, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;.;.;.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D
PROVEAN
Uncertain
D;N;.;.;.;N;N
REVEL
Pathogenic
Sift
Pathogenic
D;D;.;.;.;D;D
Sift4G
Pathogenic
D;D;.;D;.;D;D
Polyphen
0.81, 0.88
.;P;P;P;P;P;P
Vest4
0.85, 0.82, 0.85, 0.85
MutPred
Loss of phosphorylation at S4 (P = 0.1816);Loss of phosphorylation at S4 (P = 0.1816);Loss of phosphorylation at S4 (P = 0.1816);Loss of phosphorylation at S4 (P = 0.1816);Loss of phosphorylation at S4 (P = 0.1816);Loss of phosphorylation at S4 (P = 0.1816);Loss of phosphorylation at S4 (P = 0.1816);
MVP
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