rs5122
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_000483.5(APOC2):c.178G>A(p.Glu60Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000358 in 1,613,886 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E60V) has been classified as Uncertain significance.
Frequency
Consequence
NM_000483.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOC2 | NM_000483.5 | c.178G>A | p.Glu60Lys | missense_variant | 3/4 | ENST00000252490.7 | |
APOC4-APOC2 | NR_037932.1 | n.1385G>A | non_coding_transcript_exon_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOC2 | ENST00000252490.7 | c.178G>A | p.Glu60Lys | missense_variant | 3/4 | 2 | NM_000483.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00204 AC: 310AN: 152150Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000482 AC: 121AN: 250930Hom.: 1 AF XY: 0.000354 AC XY: 48AN XY: 135644
GnomAD4 exome AF: 0.000183 AC: 267AN: 1461618Hom.: 0 Cov.: 33 AF XY: 0.000184 AC XY: 134AN XY: 727112
GnomAD4 genome ? AF: 0.00204 AC: 310AN: 152268Hom.: 1 Cov.: 32 AF XY: 0.00183 AC XY: 136AN XY: 74446
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 18, 2019 | This variant is associated with the following publications: (PMID: 8490626, 31589614, 29100061) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2023 | - - |
APOLIPOPROTEIN C-II (SAN FRANCISCO) Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 1993 | - - |
Familial apolipoprotein C-II deficiency Uncertain:1
Uncertain significance, no assertion criteria provided | curation | Reproductive Health Research and Development, BGI Genomics | Jan 06, 2020 | NM_000483.4:c.178G>A in the APOC2 gene has an allele frequency of 0.007 in African subpopulation in the gnomAD database. The p.Glu60Lys (NM_000483.4:c.178G>A) was reported as Glu38Lys andd apoc-IIsf in a paper published in 1993 (PMID: 8490626), which is verified by NCBI staff. This variant has been reported in patients with hyperlipidemic. However, functional studies showed no change in enzyme activity to activate lipoprotein lipase; and apoc-IIsf had no difference in the activation energy of the enzyme compared to the normal apoc-II (PubMed: 8490626). Taken together, we interprete this variant as variant of uncertain significance (VUS). ACMG/AMP Criteria applied: BS3; PP4. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 05, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at