1-161223055-CCACACACACACACACACACACACA-CCACACACACACACA
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1
The NM_001643.2(APOA2):c.53-15_53-6delTGTGTGTGTG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,434,990 control chromosomes in the GnomAD database, including 1,176 homozygotes. 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 -10 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APOA2 | ENST00000367990.7 | c.53-15_53-6delTGTGTGTGTG | splice_region_variant, intron_variant | Intron 2 of 3 | 1 | NM_001643.2 | ENSP00000356969.3 | |||
APOA2 | ENST00000470459.6 | c.53-15_53-6delTGTGTGTGTG | splice_region_variant, intron_variant | Intron 2 of 4 | 5 | ENSP00000477031.1 |
Frequencies
GnomAD3 genomes AF: 0.109 AC: 16037AN: 147468Hom.: 988 Cov.: 0
GnomAD3 exomes AF: 0.135 AC: 26380AN: 195520Hom.: 227 AF XY: 0.137 AC XY: 14659AN XY: 106664
GnomAD4 exome AF: 0.127 AC: 182324AN: 1434990Hom.: 1176 AF XY: 0.127 AC XY: 90994AN XY: 713994
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.109 AC: 16052AN: 147580Hom.: 992 Cov.: 0 AF XY: 0.109 AC XY: 7847AN XY: 71700
ClinVar
Submissions by phenotype
not specified Benign:2
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Variant summary: APOA2 c.53-15_53-6delTGTGTGTGTG 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 0.13 in 195520 control chromosomes, predominantly at a frequency of 0.18 within the East Asian subpopulation in the gnomAD database, including 17 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 9000-fold of 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 a benign polymorphism. The variant is located in a highly polymorphic region consisting of a run of TG dinucleotide sequences. 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. -
APOA2-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at