NM_152783.5(D2HGDH):c.1370T>C (p.Leu457Pro) AND D-2-hydroxyglutaric aciduria 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 9, 2022
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:: RCV000804179.6

Allele description

NM_152783.5(D2HGDH):c.1370T>C (p.Leu457Pro)

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.1370T>C (p.Leu457Pro)

HGVS:

NC_000002.12:g.241767773T>C
NG_012012.1:g.38159T>C
NM_001287249.2:c.968T>C
NM_001352824.2:c.809T>C
NM_152783.5:c.1370T>CMANE SELECT
NP_001274178.1:p.Leu323Pro
NP_001339753.1:p.Leu270Pro
NP_689996.4:p.Leu457Pro
NC_000002.11:g.242707188T>C
NM_152783.4:c.1370T>C
NR_109778.2:n.1241T>C

Protein change:

L270P

Links:

dbSNP: rs1575352566

NCBI 1000 Genomes Browser:

rs1575352566

Molecular consequence:

NM_001287249.2:c.968T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001352824.2:c.809T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_152783.5:c.1370T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_109778.2:n.1241T>C - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000944075	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 9, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000944075

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 9, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000944075.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 649282). This missense change has been observed in individual(s) with clinical features of D2HGDH-related conditions and/or D-2-hydroxyglutaric aciduria (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 457 of the D2HGDH protein (p.Leu457Pro).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 14, 2024

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