NM_152783.5(D2HGDH):c.515G>A (p.Cys172Tyr) AND D-2-hydroxyglutaric aciduria 1

Clinical significance:Uncertain significance (Last evaluated: Mar 28, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001063278.2

Allele description [Variation Report for NM_152783.5(D2HGDH):c.515G>A (p.Cys172Tyr)]

NM_152783.5(D2HGDH):c.515G>A (p.Cys172Tyr)

Gene:
D2HGDH:D-2-hydroxyglutarate dehydrogenase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q37.3
Genomic location:
Preferred name:
NM_152783.5(D2HGDH):c.515G>A (p.Cys172Tyr)
HGVS:
  • NC_000002.12:g.241743646G>A
  • NG_012012.1:g.14032G>A
  • NM_001287249.2:c.113G>A
  • NM_001352824.2:c.-47G>A
  • NM_152783.5:c.515G>AMANE SELECT
  • NP_001274178.1:p.Cys38Tyr
  • NP_689996.4:p.Cys172Tyr
  • NC_000002.11:g.242683061G>A
  • NM_152783.4:c.515G>A
  • NR_109778.2:n.673G>A
Protein change:
C172Y
Molecular consequence:
  • NM_001352824.2:c.-47G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001287249.2:c.113G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_152783.5:c.515G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_109778.2:n.673G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
D-2-hydroxyglutaric aciduria 1 (D2HGA1)
Identifiers:
MONDO: MONDO:0024554; MedGen: C3152055; Orphanet: 79315; OMIM: 600721

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001228116Invitaecriteria provided, single submitter
Uncertain significance
(Mar 28, 2019)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria.

Kranendijk M, Struys EA, Gibson KM, Wickenhagen WV, Abdenur JE, Buechner J, Christensen E, de Kremer RD, Errami A, Gissen P, Gradowska W, Hobson E, Islam L, Korman SH, Kurczynski T, Maranda B, Meli C, Rizzo C, Sansaricq C, Trefz FK, Webster R, Jakobs C, et al.

Hum Mutat. 2010 Mar;31(3):279-83. doi: 10.1002/humu.21186.

PubMed [citation]
PMID:
20020533

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001228116.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces cysteine with tyrosine at codon 172 of the D2HGDH protein (p.Cys172Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is present in population databases (rs773735172, ExAC 0.003%). This variant has been observed in an individual affected with D-2-Hydroxyglutaric aciduria (PMID: 20020533). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Oct 7, 2021

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