rs145238683
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP3BP6BS2
The NM_000742.4(CHRNA2):c.1568C>T(p.Pro523Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,614,242 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P523Q) has been classified as Likely benign.
Frequency
Consequence
NM_000742.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA2 | NM_000742.4 | c.1568C>T | p.Pro523Leu | missense_variant | 7/7 | ENST00000407991.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA2 | ENST00000407991.3 | c.1568C>T | p.Pro523Leu | missense_variant | 7/7 | 5 | NM_000742.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251472Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135920
GnomAD4 exome AF: 0.0000520 AC: 76AN: 1461882Hom.: 0 Cov.: 30 AF XY: 0.0000523 AC XY: 38AN XY: 727244
GnomAD4 genome ? AF: 0.0000459 AC: 7AN: 152360Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74504
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 15, 2020 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; Observed in 0.0048% (12/251472 alleles) in large population cohorts (Lek et al., 2016) - |
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 18, 2020 | 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