rs567044128
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_000742.4(CHRNA2):c.1030G>A(p.Val344Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA2 | NM_000742.4 | c.1030G>A | p.Val344Ile | missense_variant | 6/7 | ENST00000407991.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA2 | ENST00000407991.3 | c.1030G>A | p.Val344Ile | missense_variant | 6/7 | 5 | NM_000742.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152098Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251198Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135786
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461868Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 727236
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74412
ClinVar
Submissions by phenotype
Autosomal dominant nocturnal frontal lobe epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 03, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CHRNA2 protein function. ClinVar contains an entry for this variant (Variation ID: 476985). This variant has not been reported in the literature in individuals affected with CHRNA2-related conditions. This variant is present in population databases (rs567044128, gnomAD 0.004%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 344 of the CHRNA2 protein (p.Val344Ile). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 21, 2021 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at