VCV000002576.1 - ClinVar

NM_000483.5(APOC2):c.270del (p.Asp91fs)

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.

(2)

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_000483.5(APOC2):c.270del (p.Asp91fs)

Variation ID: 2576 Accession: VCV000002576.1

Type and length

Deletion, 1 bp

Location

Cytogenetic: 19q13.32 19: 44949213 (GRCh38) [ NCBI UCSC ] 19: 45452470 (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	Apr 4, 2013	Apr 4, 2013	Oct 1, 1988

HGVS

Nucleotide	Protein	Molecular consequence
NM_000483.5:c.270del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000474.2:p.Asp91fs	frameshift
NR_037932.1:n.1477del		non-coding transcript variant
NC_000019.10:g.44949213del
NC_000019.9:g.45452470del
NG_008837.1:g.8228del

... more HGVS ... less HGVS

Protein change

D91fs

Other names

apoC-II Toronto

Canonical SPDI

NC_000019.10:44949212:T:

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: 608083.0004 dbSNP: rs2122211012 VarSome

Comment on variant

NCBI staff provided an HGVS expression for APOC2 Toronto based on the paper by Jiang et al., 2016. (PubMedCentral PMC4715280). The original paper by Connelly et al., 1987 (PubMed 3467353) pointed out that the deletion resulting in the observed amino acid sequence could result from either NM_000483.5:c.270del or NM_000483.5:c.271del.

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.
APOC2		-	-	GRCh38 GRCh37	2	120
APOC4-APOC2	-	-	-	GRCh38	-	121

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.
APOLIPOPROTEIN C-II (TORONTO)	Pathogenic (1)	no assertion criteria provided	Oct 1, 1988	RCV000002687.2
Familial apolipoprotein C-II deficiency	Pathogenic (1)	no assertion criteria provided	Oct 1, 1988	RCV000002688.2

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 (Oct 01, 1988)	no assertion criteria provided Method: literature only	APOLIPOPROTEIN C-II (TORONTO) Affected status: not provided Allele origin: germline	OMIM Accession: SCV000022845.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (3) PubMed: 213719‚ 3467353‚ 3225819 Comment on evidence: In subsequent studies of the family with hyperlipoproteinemia type IB (207750) reported by Cox et al. (1978), Connelly et al. (1987) identified 14 homozygotes and … (more) In subsequent studies of the family with hyperlipoproteinemia type IB (207750) reported by Cox et al. (1978), Connelly et al. (1987) identified 14 homozygotes and 23 obligate heterozygotes in the extended pedigree. Their plasma contained a unique apoC-II (designated Toronto, according to the system for hemoglobins) that had an apparent pI of 5.54 instead of 4.88 as in normal apoC-II. It was found that the sequence of apoC-II(Toronto) was identical to that of normal apoC-II from residues 1-68. It differs from residue 69, where asp69-gln70-val71-leu72-ser73-val74-leu75-lys76-gly77-glu78-glu79 is replaced by thr69-lys70-phe71-phe72-leu73-cys74. This change is consistent with the deletion of a nucleotide in the codon for either thr68 or asp69 and a resulting translation reading frameshift. Thus, it show similarities to apoC-II(St. Michael). In the apoC-II(Toronto), Cox et al. (1988) demonstrated a deletion of 1 base in the codon for amino acid threonine-68, causing an alteration of 6 amino acids and a premature termination of the protein at amino acid 74. (less)
Pathogenic (Oct 01, 1988)	no assertion criteria provided Method: literature only	HYPERLIPOPROTEINEMIA, TYPE IB Affected status: not provided Allele origin: germline	OMIM Accession: SCV000022846.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (3) PubMed: 213719‚ 3467353‚ 3225819 Comment on evidence: In subsequent studies of the family with hyperlipoproteinemia type IB (207750) reported by Cox et al. (1978), Connelly et al. (1987) identified 14 homozygotes and … (more) In subsequent studies of the family with hyperlipoproteinemia type IB (207750) reported by Cox et al. (1978), Connelly et al. (1987) identified 14 homozygotes and 23 obligate heterozygotes in the extended pedigree. Their plasma contained a unique apoC-II (designated Toronto, according to the system for hemoglobins) that had an apparent pI of 5.54 instead of 4.88 as in normal apoC-II. It was found that the sequence of apoC-II(Toronto) was identical to that of normal apoC-II from residues 1-68. It differs from residue 69, where asp69-gln70-val71-leu72-ser73-val74-leu75-lys76-gly77-glu78-glu79 is replaced by thr69-lys70-phe71-phe72-leu73-cys74. This change is consistent with the deletion of a nucleotide in the codon for either thr68 or asp69 and a resulting translation reading frameshift. Thus, it show similarities to apoC-II(St. Michael). In the apoC-II(Toronto), Cox et al. (1988) demonstrated a deletion of 1 base in the codon for amino acid threonine-68, causing an alteration of 6 amino acids and a premature termination of the protein at amino acid 74. (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
A deletion of one nucleotide results in functional deficiency of apolipoprotein CII (apo CII Toronto).	Cox DW	Journal of medical genetics	1988	PMID: 3225819
Structure of apolipoprotein C-IIToronto, a nonfunctional human apolipoprotein.	Connelly PW	Proceedings of the National Academy of Sciences of the United States of America	1987	PMID: 3467353
Inheritance of apolipoprotein C-II deficiency with hypertriglyceridemia and pancreatitis.	Cox DW	The New England journal of medicine	1978	PMID: 213719

Text-mined citations for rs2122211012 ...

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_000483.5(APOC2):c.270del (p.Asp91fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs2122211012 ...