chr2-165314005-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP2PP3_ModeratePP5
The NM_001040142.2(SCN2A):c.1280C>A(p.Ala427Asp) variant causes a missense 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. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A427V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001040142.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.1280C>A | p.Ala427Asp | missense_variant | Exon 10 of 27 | 5 | NM_001040142.2 | ENSP00000364586.2 | ||
SCN2A | ENST00000631182.3 | c.1280C>A | p.Ala427Asp | missense_variant | Exon 10 of 27 | 5 | NM_001371246.1 | ENSP00000486885.1 | ||
SCN2A | ENST00000283256.10 | c.1280C>A | p.Ala427Asp | missense_variant | Exon 10 of 27 | 1 | ENSP00000283256.6 | |||
SCN2A | ENST00000424833.5 | c.1280C>A | p.Ala427Asp | missense_variant | Exon 10 of 11 | 1 | ENSP00000406454.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be in the cytoplasmic loop between the first and second homologous domains; This variant is associated with the following publications: (PMID: 37578743, O'Connor2023[Case report]) -
- -
Complex neurodevelopmental disorder Other:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at