rs141153302
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2
The NM_001040142.2(SCN2A):c.4257C>T(p.Ala1419=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000073 in 1,603,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001040142.2 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN2A | NM_001040142.2 | c.4257C>T | p.Ala1419= | splice_region_variant, synonymous_variant | 23/27 | ENST00000375437.7 | |
SCN2A | NM_001371246.1 | c.4257C>T | p.Ala1419= | splice_region_variant, synonymous_variant | 23/27 | ENST00000631182.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.4257C>T | p.Ala1419= | splice_region_variant, synonymous_variant | 23/27 | 5 | NM_001040142.2 | P1 | |
SCN2A | ENST00000631182.3 | c.4257C>T | p.Ala1419= | splice_region_variant, synonymous_variant | 23/27 | 5 | NM_001371246.1 |
Frequencies
GnomAD3 genomes ? AF: 0.000396 AC: 60AN: 151380Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000109 AC: 27AN: 248652Hom.: 0 AF XY: 0.0000968 AC XY: 13AN XY: 134340
GnomAD4 exome AF: 0.0000393 AC: 57AN: 1451798Hom.: 0 Cov.: 29 AF XY: 0.0000402 AC XY: 29AN XY: 722064
GnomAD4 genome ? AF: 0.000396 AC: 60AN: 151496Hom.: 0 Cov.: 32 AF XY: 0.000352 AC XY: 26AN XY: 73966
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 25, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 01, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 08, 2015 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 05, 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 07, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at