NM_004588.5:c.625_626delAAinsCC
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_004588.5(SCN2B):c.625_626delAAinsCC(p.Asn209Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004588.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN2B | ENST00000278947.6 | c.625_626delAAinsCC | p.Asn209Pro | missense_variant | 1 | NM_004588.5 | ENSP00000278947.5 | |||
SCN2B | ENST00000658882.1 | n.*450_*451delAAinsCC | non_coding_transcript_exon_variant | Exon 5 of 5 | ENSP00000499572.1 | |||||
SCN2B | ENST00000669850.1 | n.867_868delAAinsCC | non_coding_transcript_exon_variant | Exon 4 of 4 | ||||||
SCN2B | ENST00000658882.1 | n.*450_*451delAAinsCC | 3_prime_UTR_variant | Exon 5 of 5 | ENSP00000499572.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Atrial fibrillation, familial, 14 Uncertain:1
This sequence change replaces asparagine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 209 of the SCN2B protein (p.Asn209Pro). This variant is present in population databases (no rsID available, gnomAD 0.02%). This missense change has been observed in individual(s) with epilepsy (PMID: 10976944). ClinVar contains an entry for this variant (Variation ID: 422854). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
not provided Uncertain:1
Identified in a patient with juvenile myoclonic epilepsy (JME), but did not segregate with disease in an affected sibling (Haug et al., 2000); In silico analysis supports that this variant does not alter protein structure/function; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015); This variant is associated with the following publications: (PMID: 10976944) -
Cardiovascular phenotype Benign:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at