rs201680546
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001040142.2(SCN2A):āc.1536A>Gā(p.Glu512=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,076 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 0.000046 ( 0 hom., cov: 33)
Exomes š: 0.000022 ( 0 hom. )
Consequence
SCN2A
NM_001040142.2 synonymous
NM_001040142.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0220
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 2-165315623-A-G is Benign according to our data. Variant chr2-165315623-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 139028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-165315623-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.022 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000046 (7/152294) while in subpopulation AMR AF= 0.000392 (6/15308). AF 95% confidence interval is 0.00017. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN2A | NM_001040142.2 | c.1536A>G | p.Glu512= | synonymous_variant | 11/27 | ENST00000375437.7 | |
SCN2A | NM_001371246.1 | c.1536A>G | p.Glu512= | synonymous_variant | 11/27 | ENST00000631182.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.1536A>G | p.Glu512= | synonymous_variant | 11/27 | 5 | NM_001040142.2 | P1 | |
SCN2A | ENST00000631182.3 | c.1536A>G | p.Glu512= | synonymous_variant | 11/27 | 5 | NM_001371246.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152176Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000443 AC: 11AN: 248448Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134522
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GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461782Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727184
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152294Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74480
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 29, 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. - |
Seizures, benign familial infantile, 3;C3150987:Developmental and epileptic encephalopathy, 11 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 07, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | SCN2A: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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