chr8-27463633-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_000742.4(CHRNA2):āc.810C>Gā(p.Ile270Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I270T) has been classified as Uncertain significance.
Frequency
Consequence
NM_000742.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA2 | NM_000742.4 | c.810C>G | p.Ile270Met | missense_variant | 6/7 | ENST00000407991.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA2 | ENST00000407991.3 | c.810C>G | p.Ile270Met | missense_variant | 6/7 | 5 | NM_000742.4 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251456Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135918
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461894Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727248
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Autosomal dominant nocturnal frontal lobe epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 08, 2021 | This variant has not been reported in the literature in individuals with CHRNA2-related disease. 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with methionine at codon 270 of the CHRNA2 protein (p.Ile270Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. - |
Autosomal dominant nocturnal frontal lobe epilepsy 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 02, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at