VCV001120051.1 - ClinVar

NM_005518.4(HMGCS2):c.72dup (p.Pro25fs)

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

NM_005518.4(HMGCS2):c.72dup (p.Pro25fs)

Variation ID: 1120051 Accession: VCV001120051.1

Type and length

Duplication, 1 bp

Location

Cytogenetic: 1p12 1: 120311395-120311396 (GRCh37) [ NCBI UCSC ] 1: 119768772-119768773 (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	May 29, 2021	May 29, 2021	May 27, 2018

HGVS

Nucleotide	Protein	Molecular consequence
NM_005518.4:c.72dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005509.1:p.Pro25fs	frameshift
NM_001166107.1:c.72dup	NP_001159579.1:p.Pro25fs	frameshift
NC_000001.11:g.119768773dup
NC_000001.10:g.120311396dup
NG_013348.1:g.5160dup
LRG_447:g.5160dup
LRG_447t1:c.72dup
LRG_447t2:c.72dup	LRG_447p2:p.Pro25fs

... more HGVS ... less HGVS

Protein change

P25fs

Other names

Canonical SPDI

NC_000001.11:119768772:T:TT

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

dbSNP: rs2101283564 VarSome

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.
HMGCS2		-	-	GRCh38 GRCh37	280	312
LOC122094910	-	-	-	GRCh38	-	15

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.
3-hydroxy-3-methylglutaryl-CoA synthase deficiency	Pathogenic (1)	no assertion criteria provided	May 27, 2018	RCV001449675.1

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 (May 27, 2018)	no assertion criteria provided Method: clinical testing	3-hydroxy-3-methylglutaryl-CoA synthase deficiency (Autosomal recessive inheritance) Affected status: yes Allele origin: maternal	IRCCS Fondazione Stella Maris, University of Pisa Accession: SCV001652910.1 First in ClinVar: May 29, 2021 Last updated: May 29, 2021	Publications: PubMed (1) PubMed: 33045405 Clinical Features: Cerebellar ataxia (present) Age: 0-9 years Sex: male Geographic origin: Europe

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
Expanding phenotypic and mutational spectra of mitochondrial HMG-CoA synthase deficiency.	Rojnueangnit K	European journal of medical genetics	2020	PMID: 33045405

Text-mined citations for rs2101283564 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Dec 25, 2023

ClinVar Genomic variation as it relates to human health

NM_005518.4(HMGCS2):c.72dup (p.Pro25fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs2101283564 ...