rs543538780
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001040142.2(SCN2A):c.1725G>A(p.Ala575=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000328 in 1,614,144 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A575A) has been classified as Likely benign.
Frequency
Consequence
NM_001040142.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN2A | NM_001040142.2 | c.1725G>A | p.Ala575= | synonymous_variant | 12/27 | ENST00000375437.7 | |
SCN2A | NM_001371246.1 | c.1725G>A | p.Ala575= | synonymous_variant | 12/27 | ENST00000631182.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.1725G>A | p.Ala575= | synonymous_variant | 12/27 | 5 | NM_001040142.2 | P1 | |
SCN2A | ENST00000631182.3 | c.1725G>A | p.Ala575= | synonymous_variant | 12/27 | 5 | NM_001371246.1 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000689 AC: 173AN: 251268Hom.: 3 AF XY: 0.000920 AC XY: 125AN XY: 135806
GnomAD4 exome AF: 0.000347 AC: 507AN: 1461886Hom.: 6 Cov.: 32 AF XY: 0.000477 AC XY: 347AN XY: 727240
GnomAD4 genome ? AF: 0.000144 AC: 22AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74450
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 05, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 19, 2015 | 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 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
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Seizures, benign familial infantile, 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at