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NM_002541.4(OGDH):c.959A>G (p.Asn320Ser) AND Oxoglutaricaciduria

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 30, 2023
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001806691.2

Allele description [Variation Report for NM_002541.4(OGDH):c.959A>G (p.Asn320Ser)]

NM_002541.4(OGDH):c.959A>G (p.Asn320Ser)

Gene:
OGDH:oxoglutarate dehydrogenase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p13
Genomic location:
Preferred name:
NM_002541.4(OGDH):c.959A>G (p.Asn320Ser)
Other names:
N320S
HGVS:
  • NC_000007.14:g.44675201A>G
  • NG_023260.1:g.73680A>G
  • NM_001003941.3:c.959A>G
  • NM_001165036.2:c.947A>G
  • NM_001363523.2:c.992A>G
  • NM_002541.4:c.959A>GMANE SELECT
  • NP_001003941.1:p.Asn320Ser
  • NP_001158508.1:p.Asn316Ser
  • NP_001350452.1:p.Asn331Ser
  • NP_002532.2:p.Asn320Ser
  • NC_000007.13:g.44714800A>G
  • NM_002541.3:c.959A>G
Protein change:
N316S; ASN320SER
Links:
OMIM: 613022.0001; dbSNP: rs2116163953
NCBI 1000 Genomes Browser:
rs2116163953
Molecular consequence:
  • NM_001003941.3:c.959A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165036.2:c.947A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363523.2:c.992A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002541.4:c.959A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Oxoglutaricaciduria
Synonyms:
Alpha-ketoglutarate dehydrogenase deficiency; Alpha KGD deficiency; 2 alpha ketoglutarate dehydrogenase deficiency
Identifiers:
MONDO: MONDO:0008759; MedGen: C2752074; Orphanet: 31; OMIM: 203740

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002050693OMIM
no assertion criteria provided
Pathogenic
(Jan 30, 2023) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A biallelic pathogenic variant in the OGDH gene results in a neurological disorder with features of a mitochondrial disease.

Yap ZY, Strucinska K, Matsuzaki S, Lee S, Si Y, Humphries K, Tarnopolsky MA, Yoon WH.

J Inherit Metab Dis. 2021 Mar;44(2):388-400. doi: 10.1002/jimd.12248. Epub 2020 Jun 24.

PubMed [citation]
PMID:
32383294
PMCID:
PMC7647956

Details of each submission

From OMIM, SCV002050693.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 2 Syrian sibs, born to consanguineous parents, with oxoglutarate dehydrogenase deficiency (OGDHD; 203740), Yap et al. (2021) identified homozygosity for a c.959A-G transition (c.959A-G, NM_002541.3) in exon 8 of the OGDH gene, resulting in an asn320-to-ser (N320S) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was present in heterozygous state in both parents and 3 unaffected sibs. The mutation was not present in the ExAC and gnomAD databases. Studies in fibroblasts from one of the sibs demonstrated reduced OGDH protein expression and activity compared to controls. HEK293 cells transfected with OGDH containing the N320S mutation showed reduced OGDH protein expression compared to cells transfected with wildtype OGDH. Yap et al. (2021) also showed that expression of wildtype human OGDH rescued embryonic lethality in Ogdh-deficient Drosophila, but human OGDH with the N320S mutation did not rescue the lethality.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 24, 2023