NM_000384.3(APOB):c.819-2A>G AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 17, 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:: RCV001851949.14

Allele description [Variation Report for NM_000384.3(APOB):c.819-2A>G]

NM_000384.3(APOB):c.819-2A>G

Gene:

APOB:apolipoprotein B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p24.1

Genomic location:

Preferred name:

NM_000384.3(APOB):c.819-2A>G

HGVS:

NC_000002.12:g.21034903T>C
NG_011793.1:g.14171A>G
NG_011793.2:g.14170A>G
NM_000384.3:c.819-2A>GMANE SELECT
NC_000002.11:g.21257775T>C

Nucleotide change:

IVS7AS, A-G, -2

Links:

OMIM: 107730.0018; dbSNP: rs1572800245

NCBI 1000 Genomes Browser:

rs1572800245

Molecular consequence:

NM_000384.3:c.819-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Hypercholesterolemia, autosomal dominant, type B (FHCL2)
Synonyms:: APOLIPOPROTEIN B-100, FAMILIAL DEFECTIVE; APOLIPOPROTEIN B-100, FAMILIAL LIGAND-DEFECTIVE; HYPERCHOLESTEROLEMIA, FAMILIAL, DUE TO LIGAND-DEFECTIVE APOLIPOPROTEIN B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007751; MedGen: C1704417; OMIM: 144010

Name:: Familial hypobetalipoproteinemia 1
Synonyms:: Hypobetalipoproteinemia, normotriglyceridemic; Acanthocytosis with hypobetalipoproteinemia
Identifiers:: MONDO: MONDO:0014252; MedGen: C4551990; OMIM: 615558

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002286137	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jul 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11940084, 16199547, 20032471, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002286137

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jul 17, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Acanthocytosis in a patient with homozygous familial hypobetalipoproteinemia due to a novel APOB splice site mutation.

Hegele RA, Miskie BA.

Clin Genet. 2002 Feb;61(2):101-3.

PubMed [citation]

PMID:: 11940084

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002286137.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 17898). Disruption of this splice site has been observed in individual(s) with homozygous familial hypobetalipoproteinemia (PMID: 11940084). This sequence change affects an acceptor splice site in intron 7 of the APOB gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in APOB are known to be pathogenic (PMID: 20032471).

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

Last Updated: Mar 5, 2025

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