chr2-241734689-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_152783.5(D2HGDH):c.-99A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 151,422 control chromosomes in the GnomAD database, including 38,412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.70 ( 38336 hom., cov: 33)
Exomes 𝑓: 0.67 ( 76 hom. )
Consequence
D2HGDH
NM_152783.5 5_prime_UTR
NM_152783.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0930
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 2-241734689-A-G is Benign according to our data. Variant chr2-241734689-A-G is described in ClinVar as [Benign]. Clinvar id is 335307.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
D2HGDH | NM_152783.5 | c.-99A>G | 5_prime_UTR_variant | 1/10 | ENST00000321264.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
D2HGDH | ENST00000321264.9 | c.-99A>G | 5_prime_UTR_variant | 1/10 | 1 | NM_152783.5 | P1 | ||
ENST00000400768.2 | downstream_gene_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.702 AC: 106041AN: 150978Hom.: 38277 Cov.: 33
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GnomAD4 exome AF: 0.670 AC: 225AN: 336Hom.: 76 Cov.: 0 AF XY: 0.672 AC XY: 164AN XY: 244
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GnomAD4 genome ? AF: 0.703 AC: 106151AN: 151086Hom.: 38336 Cov.: 33 AF XY: 0.705 AC XY: 51980AN XY: 73778
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
D-2-hydroxyglutaric aciduria 1 Benign:1
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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at