VCV002424629.5 - ClinVar

NC_000002.11:g.(?_71004499)_(74779761_?)del

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.

(3)

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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000002.11:g.(?_71004499)_(74779761_?)del

Variation ID: 2424629 Accession: VCV002424629.5

Type and length

Deletion, 3,775,263 bp

Location

Cytogenetic: 2p13.3-13.1 2: 71004499-74779761 (GRCh37) [ 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	Feb 13, 2023	Nov 11, 2023	Apr 8, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NC_000002.11:g.(?_71004499)_(74779761_?)del

Protein change

Other names

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

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.
ACTG2		-	-	GRCh38 GRCh37	91	107
ALMS1		-	-	GRCh38 GRCh38 GRCh37	6268	6588
ANKRD53		-	-	GRCh38 GRCh37	66	81
ATP6V1B1		-	-	GRCh38 GRCh37	694	759
AUP1		-	-	GRCh38 GRCh37	26	65
BOLA3		-	-	GRCh38 GRCh37	86	107
C2orf78	-	-	-	GRCh38 GRCh38 GRCh37	6	20
C2orf81	-	-	-	GRCh38 GRCh37	4	20
CCDC142	-	-	-	GRCh38 GRCh37	51	82
CCT7		-	-	GRCh38 GRCh37	35	49

There are 47 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh37).

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.
not provided	no classifications from unflagged records (1)	no classifications from unflagged records	-	RCV003107716.6
Dystonic disorder	no classifications from unflagged records (1)	no classifications from unflagged records	-	RCV003113211.6
Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Pathogenic (1)	criteria provided, single submitter	Apr 8, 2022	RCV003113210.4

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 (Apr 08, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003795744.2 First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023	Publications: PubMed (3) PubMed: 16697227‚ 16752391‚ 30682498 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the MCEE gene has been identified. Loss-of-function variants in MCEE are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the MCEE gene has been identified. Loss-of-function variants in MCEE are known to be pathogenic (PMID: 16697227, 16752391, 30682498). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with MCEE-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Apr 08, 2022)	Flagged submission flagged submission (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing Reason: This record appears to be redundant with a more recent record from the same submitter. Notes: SCV003791293 appears to (...more) Source: NCBI	Dystonic disorder Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003791293.2 First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023	Publications: PubMed (1) PubMed: 22522443 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the SPR gene has been identified. Loss-of-function variants in SPR are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the SPR gene has been identified. Loss-of-function variants in SPR are known to be pathogenic (PMID: 22522443). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with SPR-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Apr 08, 2022)	Flagged submission flagged submission (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing Reason: This record appears to be redundant with a more recent record from the same submitter. Notes: SCV003791500 appears to (...more) Source: NCBI	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003791500.2 First in ClinVar: Feb 13, 2023 Last updated: Nov 11, 2023	Publications: PubMed (1) PubMed: 23542699 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the STAMBP gene has been identified. Loss-of-function variants in STAMBP are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the STAMBP gene has been identified. Loss-of-function variants in STAMBP are known to be pathogenic (PMID: 23542699). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with STAMBP-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the MCEE gene has been identified. Loss-of-function variants in MCEE are known to be pathogenic (PMID: 16697227, 16752391, 30682498). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with MCEE-related conditions. For these reasons, this variant has been classified as Pathogenic.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the SPR gene has been identified. Loss-of-function variants in SPR are known to be pathogenic (PMID: 22522443). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with SPR-related conditions. For these reasons, this variant has been classified as Pathogenic.

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the STAMBP gene has been identified. Loss-of-function variants in STAMBP are known to be pathogenic (PMID: 23542699). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals affected with STAMBP-related conditions. For these reasons, this variant has been classified as Pathogenic.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency.	Heuberger K	Biochimica et biophysica acta. Molecular basis of disease	2019	PMID: 30682498
Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome.	McDonell LM	Nature genetics	2013	PMID: 23542699
Sepiapterin reductase deficiency: a treatable mimic of cerebral palsy.	Friedman J	Annals of neurology	2012	PMID: 22522443
A homozygous nonsense mutation in the methylmalonyl-CoA epimerase gene (MCEE) results in mild methylmalonic aciduria.	Bikker H	Human mutation	2006	PMID: 16752391
Homozygous nonsense mutation in the MCEE gene and siRNA suppression of methylmalonyl-CoA epimerase expression: a novel cause of mild methylmalonic aciduria.	Dobson CM	Molecular genetics and metabolism	2006	PMID: 16697227

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NC_000002.11:g.(?_71004499)_(74779761_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...