rs201921601
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_152783.5(D2HGDH):c.1184G>A(p.Arg395Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,613,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R395W) has been classified as Likely benign.
Frequency
Consequence
NM_152783.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
D2HGDH | NM_152783.5 | c.1184G>A | p.Arg395Gln | missense_variant | 9/10 | ENST00000321264.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
D2HGDH | ENST00000321264.9 | c.1184G>A | p.Arg395Gln | missense_variant | 9/10 | 1 | NM_152783.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000276 AC: 42AN: 152226Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000717 AC: 18AN: 251064Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135784
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1460832Hom.: 0 Cov.: 36 AF XY: 0.0000330 AC XY: 24AN XY: 726590
GnomAD4 genome ? AF: 0.000276 AC: 42AN: 152344Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74490
ClinVar
Submissions by phenotype
D-2-hydroxyglutaric aciduria 1 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jul 16, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 29, 2014 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 12, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at