1-161223055-CCACACACACACACACACACACACA-CCACACACACACACACACACACACACA
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP6_Very_StrongBS1BS2_Supporting
The NM_001643.2(APOA2):c.53-7_53-6dupTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_001643.2 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APOA2 | ENST00000367990.7 | c.53-7_53-6dupTG | splice_region_variant, intron_variant | Intron 2 of 3 | 1 | NM_001643.2 | ENSP00000356969.3 | |||
APOA2 | ENST00000470459.6 | c.53-7_53-6dupTG | splice_region_variant, intron_variant | Intron 2 of 4 | 5 | ENSP00000477031.1 |
Frequencies
GnomAD3 genomes AF: 0.0321 AC: 4735AN: 147472Hom.: 83 Cov.: 0
GnomAD4 exome AF: 0.0323 AC: 46216AN: 1430914Hom.: 5 Cov.: 0 AF XY: 0.0321 AC XY: 22830AN XY: 712064
GnomAD4 genome AF: 0.0321 AC: 4733AN: 147584Hom.: 83 Cov.: 0 AF XY: 0.0321 AC XY: 2300AN XY: 71702
ClinVar
Submissions by phenotype
not provided Benign:3
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not specified Benign:2
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Variant summary: APOA2 c.53-7_53-6dupTG alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.036 in 28768 control chromosomes in the gnomAD database, including 28 homozygotes. The observed variant frequency is approximately 1823-folds over the estimated maximal expected allele frequency for a pathogenic variant in APOA2 causing Early Onset Coronary Artery Disease phenotype (2e-05), strongly suggesting that the variant is benign. Co-occurrences with other pathogenic variant(s) have been reported (LDLR c.1567G>A, p.Val523Met). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at