rs765909421
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PP2PP3BP6BS1BS2
The NM_001040142.2(SCN2A):āc.3598A>Gā(p.Thr1200Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000551 in 1,614,050 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T1200T) has been classified as Likely benign.
Frequency
Consequence
NM_001040142.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN2A | NM_001040142.2 | c.3598A>G | p.Thr1200Ala | missense_variant | 19/27 | ENST00000375437.7 | |
SCN2A | NM_001371246.1 | c.3598A>G | p.Thr1200Ala | missense_variant | 19/27 | ENST00000631182.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.3598A>G | p.Thr1200Ala | missense_variant | 19/27 | 5 | NM_001040142.2 | P1 | |
SCN2A | ENST00000631182.3 | c.3598A>G | p.Thr1200Ala | missense_variant | 19/27 | 5 | NM_001371246.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251408Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135878
GnomAD4 exome AF: 0.0000588 AC: 86AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.0000591 AC XY: 43AN XY: 727222
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 12, 2021 | This variant is associated with the following publications: (PMID: 15048894) - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2018 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 22, 2015 | - - |
Seizures, benign familial infantile, 3;C3150987:Developmental and epileptic encephalopathy, 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1200 of the SCN2A protein (p.Thr1200Ala). This variant is present in population databases (rs765909421, gnomAD 0.009%). This missense change has been observed in individual(s) with benign familial infantile seizures (PMID: 15048894). ClinVar contains an entry for this variant (Variation ID: 212127). 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 expected to disrupt SCN2A protein function with a positive predictive value of 95%. 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 10, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at