rs796053205
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_001040142.2(SCN2A):c.1861C>A(p.Arg621Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R621C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001040142.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN2A | NM_001040142.2 | c.1861C>A | p.Arg621Ser | missense_variant | 12/27 | ENST00000375437.7 | |
SCN2A | NM_001371246.1 | c.1861C>A | p.Arg621Ser | missense_variant | 12/27 | ENST00000631182.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.1861C>A | p.Arg621Ser | missense_variant | 12/27 | 5 | NM_001040142.2 | P1 | |
SCN2A | ENST00000631182.3 | c.1861C>A | p.Arg621Ser | missense_variant | 12/27 | 5 | NM_001371246.1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727242
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Seizures, benign familial infantile, 3;C3150987:Developmental and epileptic encephalopathy, 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 28, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SCN2A protein function. This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 621 of the SCN2A protein (p.Arg621Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at