rs138497939
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 3P and 13B. PM1PP2BP4_StrongBP6BS1BS2
The NM_001040142.2(SCN2A):āc.5468A>Cā(p.Asp1823Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,614,062 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. D1823N) has been classified as Uncertain significance.
Frequency
Consequence
NM_001040142.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN2A | NM_001040142.2 | c.5468A>C | p.Asp1823Ala | missense_variant | 27/27 | ENST00000375437.7 | |
SCN2A | NM_001371246.1 | c.5468A>C | p.Asp1823Ala | missense_variant | 27/27 | ENST00000631182.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.5468A>C | p.Asp1823Ala | missense_variant | 27/27 | 5 | NM_001040142.2 | P1 | |
SCN2A | ENST00000631182.3 | c.5468A>C | p.Asp1823Ala | missense_variant | 27/27 | 5 | NM_001371246.1 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000263 AC: 66AN: 251248Hom.: 0 AF XY: 0.000280 AC XY: 38AN XY: 135792
GnomAD4 exome AF: 0.000122 AC: 179AN: 1461844Hom.: 1 Cov.: 33 AF XY: 0.000133 AC XY: 97AN XY: 727220
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74410
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 16, 2014 | - - |
Developmental and epileptic encephalopathy, 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Feb 24, 2021 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 19, 2017 | 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. - |
Seizures, benign familial infantile, 3;C3150987:Developmental and epileptic encephalopathy, 11 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 24, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at