rs140417984
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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):c.5757C>T(p.Tyr1919=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,613,902 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000085 ( 2 hom. )
Consequence
SCN2A
NM_001040142.2 synonymous
NM_001040142.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0980
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=-0.48).
BP6
Variant 2-165389563-C-T is Benign according to our data. Variant chr2-165389563-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 139021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-165389563-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.098 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000637 (97/152186) while in subpopulation AFR AF= 0.00219 (91/41532). AF 95% confidence interval is 0.00183. There are 0 homozygotes in gnomad4. There are 35 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 97 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN2A | NM_001040142.2 | c.5757C>T | p.Tyr1919= | synonymous_variant | 27/27 | ENST00000375437.7 | |
SCN2A | NM_001371246.1 | c.5757C>T | p.Tyr1919= | synonymous_variant | 27/27 | ENST00000631182.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN2A | ENST00000375437.7 | c.5757C>T | p.Tyr1919= | synonymous_variant | 27/27 | 5 | NM_001040142.2 | P1 | |
SCN2A | ENST00000631182.3 | c.5757C>T | p.Tyr1919= | synonymous_variant | 27/27 | 5 | NM_001371246.1 |
Frequencies
GnomAD3 genomes AF: 0.000638 AC: 97AN: 152068Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000156 AC: 39AN: 250592Hom.: 0 AF XY: 0.0000960 AC XY: 13AN XY: 135414
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GnomAD4 exome AF: 0.0000848 AC: 124AN: 1461716Hom.: 2 Cov.: 33 AF XY: 0.0000853 AC XY: 62AN XY: 727152
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GnomAD4 genome AF: 0.000637 AC: 97AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35AN XY: 74398
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 19, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 25, 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 07, 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 19, 2024 | - - |
SCN2A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 26, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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