NM_005984.5(SLC25A1):c.844C>T (p.Arg282Cys) AND D,L-2-hydroxyglutaric aciduria

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 14, 2023
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:: RCV001801242.11

Allele description [Variation Report for NM_005984.5(SLC25A1):c.844C>T (p.Arg282Cys)]

NM_005984.5(SLC25A1):c.844C>T (p.Arg282Cys)

Gene:

SLC25A1:solute carrier family 25 member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q11.21

Genomic location:

Preferred name:

NM_005984.5(SLC25A1):c.844C>T (p.Arg282Cys)

HGVS:

NC_000022.11:g.19176222G>A
NG_033863.1:g.7642C>T
NM_001256534.2:c.865C>T
NM_001287387.2:c.535C>T
NM_005984.5:c.844C>TMANE SELECT
NP_001243463.1:p.Arg289Cys
NP_001274316.1:p.Arg179Cys
NP_005975.1:p.Arg282Cys
NP_005975.1:p.Arg282Cys
NP_005975.1:p.Arg282Cys
NC_000022.10:g.19163735G>A
NM_005984.3:c.844C>T
NM_005984.4:c.844C>T
NR_046298.3:n.768C>T
P53007:p.Arg282Cys

Protein change:

R179C; ARG282CYS

Links:

UniProtKB: P53007#VAR_069495; OMIM: 190315.0002; dbSNP: rs431905509

NCBI 1000 Genomes Browser:

rs431905509

Molecular consequence:

NM_001256534.2:c.865C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001287387.2:c.535C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005984.5:c.844C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_046298.3:n.768C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: D,L-2-hydroxyglutaric aciduria (D2L2AD)
Synonyms:: Combined D-2- and L-2-hydroxyglutaric aciduria
Identifiers:: MONDO: MONDO:0014072; MedGen: C5574940; Orphanet: 356978; OMIM: 615182

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LOC120650863 [Panicum virgatum]
LOC120650863 [Panicum virgatum]
Gene ID:120650863

Gene
LOC121369219 [Gigantopelta aegis]
LOC121369219 [Gigantopelta aegis]
Gene ID:121369219

Gene
LOC121382652 [Gigantopelta aegis]
LOC121382652 [Gigantopelta aegis]
Gene ID:121382652

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000058658	OMIM	no assertion criteria provided	Pathogenic (Apr 4, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004175826	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 14, 2023)	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

SCV000058658

OMIM

no assertion criteria provided

Pathogenic
(Apr 4, 2013)

germline

literature only

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

SCV004175826

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 14, 2023)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria.

Nota B, Struys EA, Pop A, Jansen EE, Fernandez Ojeda MR, Kanhai WA, Kranendijk M, van Dooren SJ, Bevova MR, Sistermans EA, Nieuwint AW, Barth M, Ben-Omran T, Hoffmann GF, de Lonlay P, McDonald MT, Meberg A, Muntau AC, Nuoffer JM, Parini R, Read MH, Renneberg A, et al.

Am J Hum Genet. 2013 Apr 4;92(4):627-31. doi: 10.1016/j.ajhg.2013.03.009.

PubMed [citation]

PMID:: 23561848
PMCID:: PMC3617390

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000058658.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a male who died at the age of 4 months of combined D-2- and L-2-hydroxyglutaric aciduria (D2L2AD; 615182), Nota et al. (2013) identified homozygosity for a C-to-T transition at nucleotide 844 in exon 9 of the SLC25A1 gene, resulting in an arg-to-cys substitution at codon 282 (R282C).

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

From Neuberg Centre For Genomic Medicine, NCGM, SCV004175826.1

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

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

Last Updated: Nov 10, 2024

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