NM_000483.5(APOC2):c.122A>C (p.Lys41Thr) AND not provided

Germline classification:: Uncertain significance (5 submissions)
Last evaluated:: Aug 23, 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:: RCV001551048.17

Allele description [Variation Report for NM_000483.5(APOC2):c.122A>C (p.Lys41Thr)]

NM_000483.5(APOC2):c.122A>C (p.Lys41Thr)

Genes:

APOC4-APOC2:APOC4-APOC2 readthrough (NMD candidate) [Gene - HGNC]
APOC2:apolipoprotein C2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.32

Genomic location:

Preferred name:

NM_000483.5(APOC2):c.122A>C (p.Lys41Thr)

Other names:

APOC2, LYS19THR

HGVS:

NC_000019.10:g.44948767A>C
NG_008837.1:g.7782A>C
NM_000483.5:c.122A>CMANE SELECT
NP_000474.2:p.Lys41Thr
NC_000019.9:g.45452024A>C
NM_000483.4:c.122A>C
NR_037932.1:n.1329A>C
P02655:p.Lys41Thr

Protein change:

K41T

Links:

UniProtKB: P02655#VAR_000639; OMIM: 608083.0009; dbSNP: rs120074114

NCBI 1000 Genomes Browser:

rs120074114

Molecular consequence:

NM_000483.5:c.122A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_037932.1:n.1329A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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MULTISPECIES: chloramphenicol efflux MFS transporter CmlA4 [Gammaproteobacteria]
MULTISPECIES: chloramphenicol efflux MFS transporter CmlA4 [Gammaproteobacteria]
gi|644808165|ref|WP_025368619.1|

Protein
cytochrome b, partial (mitochondrion) [Cinara pilicornis]
cytochrome b, partial (mitochondrion) [Cinara pilicornis]
gi|635263288|gb|AHZ66423.1|

Protein
cytochrome b, partial (mitochondrion) [Cinara ponderosae]
cytochrome b, partial (mitochondrion) [Cinara ponderosae]
gi|635263266|gb|AHZ66412.1|

Protein
cytochrome b, partial (mitochondrion) [Cinara pinimaritimae]
cytochrome b, partial (mitochondrion) [Cinara pinimaritimae]
gi|635263292|gb|AHZ66425.1|

Protein
zinc finger MYM-type protein 1 isoform X8 [Homo sapiens]
zinc finger MYM-type protein 1 isoform X8 [Homo sapiens]
gi|2462513724|ref|XP_054194772.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001771473	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Aug 23, 2024)	germline	clinical testing	Citation Link,
SCV001920385	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV001962819	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV003265159	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 21, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 1782747, 22135386, 24788417, 33111339, 28492532
SCV004042054	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Sep 1, 2023)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	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

An apolipoprotein CII mutation, CIILys19----Thr' identified in patients with hyperlipidemia.

Hegele RA, Connelly PW, Maguire GF, Huff MW, Leiter L, Wolfe BM, Evans AJ, Little JA.

Dis Markers. 1991 Mar-Apr;9(2):73-80.

PubMed [citation]

PMID:: 1782747

Excess of rare variants in non-genome-wide association study candidate genes in patients with hypertriglyceridemia.

Johansen CT, Wang J, McIntyre AD, Martins RA, Ban MR, Lanktree MB, Huff MW, Péterfy M, Mehrabian M, Lusis AJ, Kathiresan S, Anand SS, Yusuf S, Lee AH, Glimcher LH, Cao H, Hegele RA.

Circ Cardiovasc Genet. 2012 Feb 1;5(1):66-72. doi: 10.1161/CIRCGENETICS.111.960864. Epub 2011 Dec 1.

PubMed [citation]

PMID:: 22135386
PMCID:: PMC3288444

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV001771473.3

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

Description

Observed in the heterozygous state in individuals with renal amyloidosis, dyslipidemia, and acute myocardial infaraction (AMI) in published literature (PMID: 33111339, 30197986, 30686043, 36555767, 36325899); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 22135386, 1782747, 30686043, 34426522, 31589614, 33111339, 30197986, 36555767, 33395107, 36325899)

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

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001920385.1

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

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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001962819.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003265159.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 41 of the APOC2 protein (p.Lys41Thr). This variant is present in population databases (rs120074114, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of APOC2-related conditions (PMID: 1782747, 22135386, 24788417, 33111339). ClinVar contains an entry for this variant (Variation ID: 2581). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 CeGaT Center for Human Genetics Tuebingen, SCV004042054.11

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

Description

APOC2: PM2:Supporting, BP4

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

Last Updated: Oct 20, 2024

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