NM_000384.3(APOB):c.7537C>T (p.Arg2513Ter) AND multiple conditions

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 30, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001837448.17

Allele description [Variation Report for NM_000384.3(APOB):c.7537C>T (p.Arg2513Ter)]

NM_000384.3(APOB):c.7537C>T (p.Arg2513Ter)

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.7537C>T (p.Arg2513Ter)

HGVS:

NC_000002.12:g.21009331G>A
NG_011793.1:g.39743C>T
NM_000384.3:c.7537C>TMANE SELECT
NP_000375.3:p.Arg2513Ter
NC_000002.10:g.21085708G>A
NC_000002.11:g.21232203G>A
NM_000384.2:c.7537C>T

Protein change:

R2513*

Links:

dbSNP: rs146538280

NCBI 1000 Genomes Browser:

rs146538280

Molecular consequence:

NM_000384.3:c.7537C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000946301	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 30, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20032471, 1940616, 28733173, 28492532
SCV002778892	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 4, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000946301

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 30, 2024)

germline

clinical testing

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

SCV002778892

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 4, 2021)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Nonsynonymous mutations within APOB in human familial hypobetalipoproteinemia: evidence for feedback inhibition of lipogenesis and postendoplasmic reticulum degradation of apolipoprotein B.

Zhong S, Magnolo AL, Sundaram M, Zhou H, Yao EF, Di Leo E, Loria P, Wang S, Bamji-Mirza M, Wang L, McKnight CJ, Figeys D, Wang Y, Tarugi P, Yao Z.

J Biol Chem. 2010 Feb 26;285(9):6453-64. doi: 10.1074/jbc.M109.060467. Epub 2009 Dec 23.

PubMed [citation]

PMID:: 20032471
PMCID:: PMC2825441

ApoB-54.8, a truncated apolipoprotein found primarily in VLDL, is associated with a nonsense mutation in the apoB gene and hypobetalipoproteinemia.

Wagner RD, Krul ES, Tang J, Parhofer KG, Garlock K, Talmud P, Schonfeld G.

J Lipid Res. 1991 Jun;32(6):1001-11.

PubMed [citation]

PMID:: 1940616

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000946301.5

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

Description

This sequence change creates a premature translational stop signal (p.Arg2513*) in the APOB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APOB are known to be pathogenic (PMID: 20032471). This variant is present in population databases (rs146538280, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with autosomal dominant hypobetalipoproteinemia (PMID: 1940616, 28733173). It has also been observed to segregate with disease in related individuals. This variant is also known as 7665C>T or Arg2486X. ClinVar contains an entry for this variant (Variation ID: 69511). For these reasons, this variant has been classified as Pathogenic.

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002778892.1

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

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

Last Updated: Oct 5, 2025

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