2-165389558-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4
The NM_001040142.2(SCN2A):c.5752C>G(p.Arg1918Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
Consequence
SCN2A
NM_001040142.2 missense
NM_001040142.2 missense
Scores
1
8
10
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.04
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 Uncertain_significance. Variant got 4 ACMG points.
PM1
In a topological_domain Cytoplasmic (size 229) in uniprot entity SCN2A_HUMAN there are 7 pathogenic changes around while only 1 benign (88%) in NM_001040142.2
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SCN2A. . Trascript score misZ 8.7114 (greater than threshold 3.09). GenCC has associacion of gene with seizures, benign familial infantile, 3, Dravet syndrome, benign familial neonatal-infantile seizures, malignant migrating partial seizures of infancy, complex neurodevelopmental disorder, developmental and epileptic encephalopathy, 11, developmental and epileptic encephalopathy, West syndrome, benign familial infantile epilepsy, episodic ataxia, type 9.
BP4
Computational evidence support a benign effect (MetaRNN=0.41390577).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN2A | NM_001040142.2 | c.5752C>G | p.Arg1918Gly | missense_variant | 27/27 | ENST00000375437.7 | NP_001035232.1 | |
SCN2A | NM_001371246.1 | c.5752C>G | p.Arg1918Gly | missense_variant | 27/27 | ENST00000631182.3 | NP_001358175.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.5752C>G | p.Arg1918Gly | missense_variant | 27/27 | 5 | NM_001040142.2 | ENSP00000364586 | P1 | |
SCN2A | ENST00000631182.3 | c.5752C>G | p.Arg1918Gly | missense_variant | 27/27 | 5 | NM_001371246.1 | ENSP00000486885 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.;T;.;D;D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;.;.;.;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;.;L;L;L;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.;.;.;N;N
REVEL
Uncertain
Sift
Benign
T;.;.;.;.;T;T
Sift4G
Benign
T;.;.;T;.;T;T
Polyphen
B;B;.;B;B;B;B
Vest4
MutPred
Loss of stability (P = 0.0074);Loss of stability (P = 0.0074);.;Loss of stability (P = 0.0074);Loss of stability (P = 0.0074);Loss of stability (P = 0.0074);Loss of stability (P = 0.0074);
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