This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Benign/Likely benign
- Review status:
- criteria provided, multiple submitters, no conflicts
- Submissions:
- 8
- First in ClinVar:
- Apr 4, 2013
- Most recent Submission:
- Feb 7, 2023
- Last evaluated:
- Nov 2, 2022
- Accession:
- VCV000002573.16
- Variation ID:
- 2573
- Description:
- single nucleotide variant
Help
NM_000483.5(APOC2):c.229A>C (p.Lys77Gln)
- Allele ID
- 17612
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 19q13.32
- Genomic location
- 19: 44949172 (GRCh38) GRCh38 UCSC
- 19: 45452429 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000483.5:c.229A>C MANE Select NP_000474.2:p.Lys77Gln missense NR_037932.1:n.1436A>C NC_000019.10:g.44949172A>C NC_000019.9:g.45452429A>C NG_008837.1:g.8187A>C P02655:p.Lys77Gln - Protein change
- K77Q
- Other names
- APOC2, LYS55GLN
- Canonical SPDI
- NC_000019.10:44949171:A:C
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- 0.00779 (C)
- Allele frequency
- Exome Aggregation Consortium (ExAC) 0.00238
- The Genome Aggregation Database (gnomAD) 0.00784
- The Genome Aggregation Database (gnomAD), exomes 0.00183
- 1000 Genomes Project 0.00779
- Trans-Omics for Precision Medicine (TOPMed) 0.00825
- The Genome Aggregation Database (gnomAD) 0.00701
- Trans-Omics for Precision Medicine (TOPMed) 0.00821
- Links
- ClinGen: CA115614
- UniProtKB: P02655#VAR_000642
- OMIM: 608083.0001
- dbSNP: rs5126
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Benign/Likely benign | 2 | criteria provided, multiple submitters, no conflicts | Nov 2, 2022 | RCV000974450.8 | |
| Benign/Likely benign | 3 | criteria provided, multiple submitters, no conflicts | Oct 23, 2021 | RCV000991188.5 | |
| Benign | 1 | criteria provided, single submitter | Oct 28, 2020 | RCV001777130.1 | |
| Benign | 1 | criteria provided, single submitter | Aug 26, 2019 | RCV002444415.1 | |
|
APOLIPOPROTEIN C-II (AFRICAN)
|
Pathogenic | 1 | no assertion criteria provided | Feb 1, 1986 | RCV000002682.2 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Familial apolipoprotein C-II deficiency
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001295706.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
|
Likely benign
(Nov 03, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001814285.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 31589614, 33111339)
|
|
|
Benign
(Aug 26, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002734829.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA … (more)
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
|
|
|
Benign
(Nov 02, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001122273.4
First in ClinVar: Dec 17, 2019 Last updated: Feb 07, 2023 |
|
|
|
Benign
(Oct 28, 2020)
|
criteria provided, single submitter
Method: research
|
not specified
Affected status: unknown
Allele origin:
germline
|
H3Africa Consortium
Study: H3Africa
Accession: SCV002014637.1 First in ClinVar: Nov 13, 2021 Last updated: Nov 13, 2021 |
Comment:
While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.063, its frequency in African populations is >5%. This suggests that previous classifications of … (more)
While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.063, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. (less)
|
|
|
Likely benign
(Oct 23, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Familial apolipoprotein C-II deficiency
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002811419.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Benign
(Jan 06, 2020)
|
no assertion criteria provided
Method: curation
|
Hyperlipoproteinemia, type Ib
Affected status: unknown
Allele origin:
germline
|
Reproductive Health Research and Development,BGI Genomics
Accession: SCV001142491.1
First in ClinVar: Jan 12, 2020 Last updated: Jan 12, 2020 |
Comment:
NM_000483.4:c.229A>C in the APOC2 gene has an allele frequency of 0.026 in African subpopulation in the gnomAD database, including 8 homozygous occurrences. Pathogenic computational verdict … (more)
NM_000483.4:c.229A>C in the APOC2 gene has an allele frequency of 0.026 in African subpopulation in the gnomAD database, including 8 homozygous occurrences. Pathogenic computational verdict because pathogenic predictions from DANN, MutationAssessor, MutationTaster and SIFTT. aken together, we interprete this variant as Benign/Likely benign variant. ACMG/AMP criteria applied: BS1, BS2. (less)
|
|
|
Pathogenic
(Feb 01, 1986)
|
no assertion criteria provided
Method: literature only
|
APOLIPOPROTEIN C-II (AFRICAN)
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000022840.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
Menzel et al. (1986) showed that about 12% of Americans of African ancestry have a variant of apoC-II, an isoform with substitution of glutamine for … (more)
Menzel et al. (1986) showed that about 12% of Americans of African ancestry have a variant of apoC-II, an isoform with substitution of glutamine for lysine at residue 55. This isoform could have been generated by either of 2 single-base exchanges. (less)
|
Functional evidence
Help| 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 this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Analysis of the Prader-Willi syndrome imprinting center using droplet digital PCR and next-generation whole-exome sequencing. | Hartin SN | Molecular genetics & genomic medicine | 2019 | PMID: 30793526 |
| Apolipoprotein C-II: New findings related to genetics, biochemistry, and role in triglyceride metabolism. | Wolska A | Atherosclerosis | 2017 | PMID: 29100061 |
| A variant primary structure of apolipoprotein C-II in individuals of African descent. | Menzel HJ | The Journal of clinical investigation | 1986 | PMID: 3944271 |
Text-mined citations for rs5126...
HelpThese 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 Mar 05, 2023