2-74461318-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006302.3(MOGS):c.2471G>A(p.Gly824Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,613,998 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G824S) has been classified as Uncertain significance.
Frequency
Consequence
NM_006302.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MOGS | NM_006302.3 | c.2471G>A | p.Gly824Asp | missense_variant | 4/4 | ENST00000448666.7 | |
MOGS | NM_001146158.2 | c.2153G>A | p.Gly718Asp | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MOGS | ENST00000448666.7 | c.2471G>A | p.Gly824Asp | missense_variant | 4/4 | 1 | NM_006302.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152252Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249252Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135340
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461746Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727168
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74380
ClinVar
Submissions by phenotype
MOGS-congenital disorder of glycosylation Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 824 of the MOGS protein (p.Gly824Asp). This variant is present in population databases (rs376424106, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of congenital glycosylation disorders (PMID: 33058492). 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 disruptive. 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