chr19-44948488-C-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_000483.5(APOC2):c.10C>T(p.Arg4*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 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 Likely pathogenic (★★).
Frequency
Consequence
NM_000483.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APOC2 | NM_000483.5 | c.10C>T | p.Arg4* | stop_gained | Exon 2 of 4 | ENST00000252490.7 | NP_000474.2 | |
APOC4-APOC2 | NR_037932.1 | n.1217C>T | non_coding_transcript_exon_variant | Exon 4 of 6 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152058Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251490Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135920
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461834Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727216
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152058Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74248
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34426522, 1569385) -
This sequence change creates a premature translational stop signal (p.Arg4*) in the APOC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APOC2 are known to be pathogenic (PMID: 1569385, 1971748, 26772541). This variant is present in population databases (rs202190413, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with apolipoprotein C-II deficiency (PMID: 1569385). This variant is also known as ApoC-II Paris2. ClinVar contains an entry for this variant (Variation ID: 1374052). For these reasons, this variant has been classified as Pathogenic. -
Familial apolipoprotein C-II deficiency Pathogenic:1
The observed stop gained variant c.10C>T(p.Arg4Ter) in APOC2 gene has been reported in homozygous state in an individual with apolipoprotein C-II deficiency (Parrott CL, et al., 1992). The c.10C>T variant has 0.003% allele frequency in gnomAD Exomes. This variant has been reported to the ClinVar database as Pathogenic. Computational evidence (Mutation Taster - Disease causing) predicts damaging effect on protein structure and function for this variant.This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing (Jiang J, et al.., 2016). For these reasons, this variant has been classified as Likely Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at