rs561375550
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001040142.2(SCN2A):c.2563-4C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,613,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 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, intron
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN2A | NM_001040142.2 | c.2563-4C>A | splice_region_variant, intron_variant | ENST00000375437.7 | NP_001035232.1 | |||
SCN2A | NM_001371246.1 | c.2563-4C>A | splice_region_variant, intron_variant | ENST00000631182.3 | NP_001358175.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.2563-4C>A | splice_region_variant, intron_variant | 5 | NM_001040142.2 | ENSP00000364586.2 | ||||
SCN2A | ENST00000631182.3 | c.2563-4C>A | splice_region_variant, intron_variant | 5 | NM_001371246.1 | ENSP00000486885.1 | ||||
SCN2A | ENST00000283256.10 | c.2563-4C>A | splice_region_variant, intron_variant | 1 | ENSP00000283256.6 |
Frequencies
GnomAD3 genomes AF: 0.0000921 AC: 14AN: 152030Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000957 AC: 24AN: 250768Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135790
GnomAD4 exome AF: 0.000107 AC: 157AN: 1461468Hom.: 0 Cov.: 31 AF XY: 0.000117 AC XY: 85AN XY: 727066
GnomAD4 genome AF: 0.0000921 AC: 14AN: 152030Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7AN XY: 74260
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 06, 2017 | 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. - |
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 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 27, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | SCN2A: PM2:Supporting, BP4, BP5 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at