rs186154973
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BA1BP4
This summary comes from the ClinGen Evidence Repository: The c.1571G>A variant in SCN2A is a missense variant predicted to cause substitution of Arginine by Glutamine at amino acid 524 (p.Arg524Gln). The highest population minor allele frequency in gnomAD v2.1.1 is 0.1504% (30/19942 alleles) in Asian population, which is higher than the ClinGen Epilepsy Sodium Channel VCEP threshold (0.01%) for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.192, evidence that does not predict a damaging effect on SCN2A function (BP4). In summary, this variant meets the criteria to be classified as BENIGN for autosomal dominant complex neurodevelopmental disorder based on the ACMG/AMP criteria applied, as specified by the ClinGen Epilepsy Sodium Channel VCEP: BA1 and BP4. (Version 1; approved 6/13/2023) LINK:https://erepo.genome.network/evrepo/ui/classification/CA1939839/MONDO:0100038/068
Frequency
Consequence
NM_001040142.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN2A | NM_001040142.2 | c.1571G>A | p.Arg524Gln | missense_variant | 11/27 | ENST00000375437.7 | NP_001035232.1 | |
SCN2A | NM_001371246.1 | c.1571G>A | p.Arg524Gln | missense_variant | 11/27 | ENST00000631182.3 | NP_001358175.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.1571G>A | p.Arg524Gln | missense_variant | 11/27 | 5 | NM_001040142.2 | ENSP00000364586 | P1 | |
SCN2A | ENST00000631182.3 | c.1571G>A | p.Arg524Gln | missense_variant | 11/27 | 5 | NM_001371246.1 | ENSP00000486885 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152168Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000133 AC: 33AN: 248802Hom.: 0 AF XY: 0.0000965 AC XY: 13AN XY: 134694
GnomAD4 exome AF: 0.0000568 AC: 83AN: 1461772Hom.: 0 Cov.: 32 AF XY: 0.0000509 AC XY: 37AN XY: 727172
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152286Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6AN XY: 74472
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 21, 2017 | - - |
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 | Oct 17, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at