chr4-46250444-GC-TT
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP6
The NM_000807.4(GABRA2):c.1219_1220delinsAA(p.Ala407Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A407E) has been classified as Likely benign.
Frequency
Consequence
NM_000807.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRA2 | NM_000807.4 | c.1219_1220delinsAA | p.Ala407Lys | missense_variant | 10/10 | ENST00000381620.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRA2 | ENST00000381620.9 | c.1219_1220delinsAA | p.Ala407Lys | missense_variant | 10/10 | 1 | NM_000807.4 | P2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 02, 2017 | The c.1219_1220delGCinsAA variant in the GABRA2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1219_1220delGCinsAA variant results in the replacement of the normal Alanine at position 407 with a Lysine residue, denoted p.Ala407Lys. The c.1219_1220delGCinsAA variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.1219_1220delGCinsAA variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This variant occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret c.1219_1220delGCinsAA as a variant of uncertain significance. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at