chr11-118166957-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_004588.5(SCN2B):c.578C>T(p.Thr193Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,614,176 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T193R) has been classified as Uncertain significance.
Frequency
Consequence
NM_004588.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN2B | NM_004588.5 | c.578C>T | p.Thr193Ile | missense_variant | 4/4 | ENST00000278947.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN2B | ENST00000278947.6 | c.578C>T | p.Thr193Ile | missense_variant | 4/4 | 1 | NM_004588.5 | P1 | |
SCN2B | ENST00000669850.1 | n.820C>T | non_coding_transcript_exon_variant | 4/4 | |||||
SCN2B | ENST00000658882.1 | c.*403C>T | 3_prime_UTR_variant, NMD_transcript_variant | 5/5 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251462Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135908
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461856Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727230
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74470
ClinVar
Submissions by phenotype
Atrial fibrillation, familial, 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 193 of the SCN2B protein (p.Thr193Ile). This variant is present in population databases (rs115353159, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SCN2B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1749641). 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 tolerated. 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2021 | The c.578C>T (p.T193I) alteration is located in exon 4 (coding exon 4) of the SCN2B gene. This alteration results from a C to T substitution at nucleotide position 578, causing the threonine (T) at amino acid position 193 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at