2-241734937-C-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_152783.5(D2HGDH):c.-92-196C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 393,738 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.019 ( 36 hom., cov: 34)
Exomes 𝑓: 0.021 ( 100 hom. )
Consequence
D2HGDH
NM_152783.5 intron
NM_152783.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.27
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=-0.75).
BP6
?
Variant 2-241734937-C-G is Benign according to our data. Variant chr2-241734937-C-G is described in ClinVar as [Benign]. Clinvar id is 1263894.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0192 (2920/152198) while in subpopulation NFE AF= 0.0264 (1798/67982). AF 95% confidence interval is 0.0254. There are 36 homozygotes in gnomad4. There are 1486 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 36 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
D2HGDH | NM_152783.5 | c.-92-196C>G | intron_variant | ENST00000321264.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
D2HGDH | ENST00000321264.9 | c.-92-196C>G | intron_variant | 1 | NM_152783.5 | P1 | |||
ENST00000400768.2 | n.383-133G>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0192 AC: 2920AN: 152090Hom.: 36 Cov.: 34
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GnomAD4 exome AF: 0.0213 AC: 5137AN: 241540Hom.: 100 AF XY: 0.0205 AC XY: 2539AN XY: 124032
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 11, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at