19-44948488-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000483.5(APOC2):āc.10C>Gā(p.Arg4Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_000483.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APOC2 | NM_000483.5 | c.10C>G | p.Arg4Gly | missense_variant | Exon 2 of 4 | ENST00000252490.7 | NP_000474.2 | |
APOC4-APOC2 | NR_037932.1 | n.1217C>G | non_coding_transcript_exon_variant | Exon 4 of 6 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152058Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251490Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135920
GnomAD4 exome AF: 0.0000493 AC: 72AN: 1461834Hom.: 0 Cov.: 32 AF XY: 0.0000426 AC XY: 31AN XY: 727216
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152058Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74248
ClinVar
Submissions by phenotype
Familial apolipoprotein C-II deficiency Uncertain:1
- -
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 4 of the APOC2 protein (p.Arg4Gly). This variant is present in population databases (rs202190413, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with APOC2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. -
Cardiovascular phenotype Uncertain:1
The p.R4G variant (also known as c.10C>G), located in coding exon 1 of the APOC2 gene, results from a C to G substitution at nucleotide position 10. The arginine at codon 4 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at