2-241735505-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_152783.5(D2HGDH):c.281G>C(p.Arg94Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,606,592 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 (★★).
Frequency
Consequence
NM_152783.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152264Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.0000128 AC: 3AN: 234536Hom.: 0 AF XY: 0.0000155 AC XY: 2AN XY: 128930
GnomAD4 exome AF: 0.0000268 AC: 39AN: 1454328Hom.: 0 Cov.: 38 AF XY: 0.0000332 AC XY: 24AN XY: 723968
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152264Hom.: 0 Cov.: 35 AF XY: 0.0000403 AC XY: 3AN XY: 74398
ClinVar
Submissions by phenotype
not specified Uncertain:1
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D-2-hydroxyglutaric aciduria 1 Uncertain:1
This sequence change replaces arginine with proline at codon 94 of the D2HGDH protein (p.Arg94Pro). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and proline. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with D-2-hydroxyglutaric aciduria (Invitae). ClinVar contains an entry for this variant (Variation ID: 210818). This variant is not present in population databases (ExAC no frequency). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at