VCV000001611.2 - ClinVar

L2HGDH, EX1-9DEL

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

L2HGDH, EX1-9DEL

Variation ID: 1611 Accession: VCV000001611.2

Type and length

Deletion, 247,255 bp

Location

Cytogenetic: 14q21.3 14: 50000000-50247254 (GRCh38) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jan 10, 2020	Jan 10, 2020	Nov 15, 2004

HGVS

Nucleotide	Protein	Molecular consequence
NC_000014.9:g.(50000000_?)_(?_50247254)del

Protein change

Other names

L2HGDH, EX1-9DEL
EX1-9 DEL

Canonical SPDI

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 609584.0005 VarSome

Comment on variant

A deletion of several hundred kb, but retaining exon 10 of L2HGDH

The authors described this deletion as 'The large deletion in family K was at least several hundred kilobases, with an absence of genomic amplification of exons 1–9, but normal amplification of exon 10 and of all the surrounding microsatellites'. To place this on the genome, ClinVar staff placed one end of the deletion at the beginning of exon 10, and the upstream end at the estimated location of 50Mbp.

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
L2HGDH		-	-	GRCh38 GRCh37	239	284
LINC01588	-	-	-	GRCh38 GRCh37	-	11
LINC01599	-	-	-	GRCh38 GRCh37	-	11
LOC125024479	-	-	-	GRCh38	-	4
LOC125024480	-	-	-	GRCh38	-	4
LOC129390630	-	-	-	GRCh38	-	7
LOC130055566	-	-	-	GRCh38	-	4
LOC130055567	-	-	-	GRCh38	-	4
LOC130055568	-	-	-	GRCh38	-	4
LOC130055569	-	-	-	GRCh38	-	4

There are 22 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh38).

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
L-2-hydroxyglutaric aciduria	Pathogenic (1)	no assertion criteria provided	Nov 15, 2004	RCV000001678.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Nov 15, 2004)	no assertion criteria provided Method: literature only	L-2-HYDROXYGLUTARIC ACIDURIA Affected status: not provided Allele origin: germline	OMIM Accession: SCV000021834.3 First in ClinVar: Apr 04, 2013 Last updated: Jan 10, 2020	Publications: PubMed (1) PubMed: 15385440 Comment on evidence: In a child of a consanguineous Turkish family with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Topcu et al. (2004) reported homozygosity for a large genomic deletion in … (more) In a child of a consanguineous Turkish family with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Topcu et al. (2004) reported homozygosity for a large genomic deletion in the L2HGDH gene that eliminated exons 1 through 9. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
L-2-Hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1.	Topçu M	Human molecular genetics	2004	PMID: 15385440

Text-mined citations for this variant ...

Record last updated Oct 15, 2023

ClinVar Genomic variation as it relates to human health

L2HGDH, EX1-9DEL

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...