rs201685102
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001040142.2(SCN2A):āc.879T>Gā(p.Thr293=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,613,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00017 ( 0 hom., cov: 32)
Exomes š: 0.00010 ( 0 hom. )
Consequence
SCN2A
NM_001040142.2 synonymous
NM_001040142.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.33
Genes affected
SCN2A (HGNC:10588): (sodium voltage-gated channel alpha subunit 2) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with four repeat domains, each of which is composed of six membrane-spanning segments, and one or more regulatory beta subunits. Voltage-gated sodium channels function in the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. Allelic variants of this gene are associated with seizure disorders and autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 2-165310504-T-G is Benign according to our data. Variant chr2-165310504-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 416519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.33 with no splicing effect.
BS2
?
High AC in GnomAd4 at 26 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN2A | NM_001040142.2 | c.879T>G | p.Thr293= | synonymous_variant | 7/27 | ENST00000375437.7 | |
SCN2A | NM_001371246.1 | c.879T>G | p.Thr293= | synonymous_variant | 7/27 | ENST00000631182.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.879T>G | p.Thr293= | synonymous_variant | 7/27 | 5 | NM_001040142.2 | P1 | |
SCN2A | ENST00000631182.3 | c.879T>G | p.Thr293= | synonymous_variant | 7/27 | 5 | NM_001371246.1 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152144Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000207 AC: 52AN: 251042Hom.: 0 AF XY: 0.000192 AC XY: 26AN XY: 135670
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GnomAD4 exome AF: 0.0000999 AC: 146AN: 1461156Hom.: 0 Cov.: 31 AF XY: 0.0000977 AC XY: 71AN XY: 726896
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GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74330
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 02, 2021 | - - |
Seizures, benign familial infantile, 3;C3150987:Developmental and epileptic encephalopathy, 11 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 13, 2023 | - - |
Seizures, benign familial infantile, 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 23, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at