rs755705607
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The ENST00000476832.2(ALG2):āc.219C>Gā(p.Asp73Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,409,948 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 ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D73H) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000476832.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALG2 | NM_033087.4 | c.219C>G | p.Asp73Glu | missense_variant | 1/2 | ENST00000476832.2 | NP_149078.1 | |
ALG2 | NR_024532.2 | n.267C>G | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALG2 | ENST00000476832.2 | c.219C>G | p.Asp73Glu | missense_variant | 1/2 | 1 | NM_033087.4 | ENSP00000417764 | P1 | |
ALG2 | ENST00000238477.5 | c.219C>G | p.Asp73Glu | missense_variant, NMD_transcript_variant | 1/3 | 2 | ENSP00000432675 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000614 AC: 1AN: 162994Hom.: 0 AF XY: 0.0000111 AC XY: 1AN XY: 90340
GnomAD4 exome AF: 0.00000213 AC: 3AN: 1409948Hom.: 0 Cov.: 32 AF XY: 0.00000430 AC XY: 3AN XY: 698130
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
ALG2-congenital disorder of glycosylation;C4015597:Congenital myasthenic syndrome 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 30, 2016 | This sequence change replaces aspartic acid with glutamic acid at codon 73 of the ALG2 protein (p.Asp73Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is present in population databases (rs755705607, ExAC 0.02%) but has not been reported in the literature in individuals with a ALG2-related disease. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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