rs111670322
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_152783.5(D2HGDH):c.1395G>A(p.Thr465Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 1,612,206 control chromosomes in the GnomAD database, including 328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.025 ( 162 hom., cov: 33)
Exomes 𝑓: 0.0026 ( 166 hom. )
Consequence
D2HGDH
NM_152783.5 synonymous
NM_152783.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.24
Genes affected
D2HGDH (HGNC:28358): (D-2-hydroxyglutarate dehydrogenase) This gene encodes D-2hydroxyglutarate dehydrogenase, a mitochondrial enzyme belonging to the FAD-binding oxidoreductase/transferase type 4 family. This enzyme, which is most active in liver and kidney but also active in heart and brain, converts D-2-hydroxyglutarate to 2-ketoglutarate. Mutations in this gene are present in D-2-hydroxyglutaric aciduria, a rare recessive neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 2-241767798-G-A is Benign according to our data. Variant chr2-241767798-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 158413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.24 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0857 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0253 AC: 3844AN: 152088Hom.: 160 Cov.: 33
GnomAD3 genomes
AF:
AC:
3844
AN:
152088
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00647 AC: 1581AN: 244238Hom.: 64 AF XY: 0.00464 AC XY: 618AN XY: 133170
GnomAD3 exomes
AF:
AC:
1581
AN:
244238
Hom.:
AF XY:
AC XY:
618
AN XY:
133170
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00262 AC: 3826AN: 1460000Hom.: 166 Cov.: 34 AF XY: 0.00229 AC XY: 1662AN XY: 726300
GnomAD4 exome
AF:
AC:
3826
AN:
1460000
Hom.:
Cov.:
34
AF XY:
AC XY:
1662
AN XY:
726300
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0254 AC: 3866AN: 152206Hom.: 162 Cov.: 33 AF XY: 0.0251 AC XY: 1865AN XY: 74428
GnomAD4 genome
AF:
AC:
3866
AN:
152206
Hom.:
Cov.:
33
AF XY:
AC XY:
1865
AN XY:
74428
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
26
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
D-2-hydroxyglutaric aciduria 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 23, 2024 | - - |
not provided Benign:2
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 16, 2016 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 31, 2013 | - - |
D2HGDH-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 30, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at