rs180849348
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_033087.4(ALG2):c.17G>T(p.Gly6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,588,790 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G6A) has been classified as Likely benign.
Frequency
Consequence
NM_033087.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG2 | NM_033087.4 | c.17G>T | p.Gly6Val | missense_variant | 1/2 | ENST00000476832.2 | |
ALG2 | NR_024532.2 | n.65G>T | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG2 | ENST00000476832.2 | c.17G>T | p.Gly6Val | missense_variant | 1/2 | 1 | NM_033087.4 | P1 | |
ALG2 | ENST00000238477.5 | c.17G>T | p.Gly6Val | missense_variant, NMD_transcript_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.96e-7 AC: 1AN: 1436564Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1AN XY: 713820
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74372
ClinVar
Submissions by phenotype
ALG2-congenital disorder of glycosylation;C4015597:Congenital myasthenic syndrome 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 6 of the ALG2 protein (p.Gly6Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1349332). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at