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NM_001289910.1(IDH2):c.263G>A (p.Arg88Gln) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 24, 2018
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000292094.1

Allele description

NM_001289910.1(IDH2):c.263G>A (p.Arg88Gln)

Gene:
IDH2:isocitrate dehydrogenase (NADP(+)) 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_001289910.1(IDH2):c.263G>A (p.Arg88Gln)
HGVS:
  • NC_000015.10:g.90088702C>T
  • NG_023302.1:g.18775G>A
  • NM_001289910.1:c.263G>A
  • NM_001290114.2:c.29G>A
  • NM_002168.3:c.419G>A
  • NP_001276839.1:p.Arg88Gln
  • NP_001277043.1:p.Arg10Gln
  • NP_002159.2:p.Arg140Gln
  • LRG_611t1:c.263G>A
  • LRG_611t2:c.419G>A
  • LRG_611:g.18775G>A
  • LRG_611p1:p.Arg88Gln
  • LRG_611p2:p.Arg140Gln
  • NC_000015.9:g.90631934C>T
  • NM_002168.2:c.419G>A
  • P48735:p.Arg140Gln
Protein change:
R10Q; ARG140GLN
Links:
UniProtKB: P48735#VAR_065175; OMIM: 147650.0001; dbSNP: rs121913502
NCBI 1000 Genomes Browser:
rs121913502
Molecular consequence:
  • NM_001289910.1:c.263G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001290114.2:c.29G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002168.3:c.419G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000329950GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Pathogenic
(May 24, 2018) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000329950.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The R140Q pathogenic variant in the IDH2 gene has been reported previously as a de novo variant in the heterozygous state in multiple individuals with D-2 hydroxyglutaric aciduria type 2 (Kranendijk et al., 2010). R140Q has also been reported as de novo in the mosaic state in an individual with D-2HGA type 2. In addition, R140Q was also reported as mosaic in the unaffected mother of an individual with D-2HGA type 2 (Kranendijk et al., 2010; Nota et al., 2013). The R140Q variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R140Q variant is a semi-conservative amino acid substitution, which occurs as a position that is conserved across species. An enzyme assay which determines IDH2 activity in lymphoblast extracts was created, and confirmed that R140Q results in gain of function in D-2 hydroxyglutaric aciduria type 2 (Kranendijk et al., 2011). We interpret R140Q as a pathogenic variant.

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

Last Updated: Sep 29, 2021