rs765714006
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001040142.2(SCN2A):āc.847C>Gā(p.Pro283Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,376 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. P283P) has been classified as Likely benign.
Frequency
Consequence
NM_001040142.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN2A | NM_001040142.2 | c.847C>G | p.Pro283Ala | missense_variant | 7/27 | ENST00000375437.7 | |
SCN2A | NM_001371246.1 | c.847C>G | p.Pro283Ala | missense_variant | 7/27 | ENST00000631182.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.847C>G | p.Pro283Ala | missense_variant | 7/27 | 5 | NM_001040142.2 | P1 | |
SCN2A | ENST00000631182.3 | c.847C>G | p.Pro283Ala | missense_variant | 7/27 | 5 | NM_001371246.1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251218Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135782
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461376Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726988
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 | Jan 25, 2024 | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 283 of the SCN2A protein (p.Pro283Ala). This variant is present in population databases (rs765714006, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 533491). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN2A protein function. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2019 | The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be within the pore forming loop between the S5 and S6 transmembrane segments of the first homologous domain - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at