chr2-189085155-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000393.5(COL5A2):c.798+5G>A variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000372 in 1,611,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000393.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.798+5G>A | splice_region_variant, intron_variant | Intron 11 of 53 | ENST00000374866.9 | NP_000384.2 | ||
COL5A2 | XM_011510573.4 | c.660+5G>A | splice_region_variant, intron_variant | Intron 14 of 56 | XP_011508875.1 | |||
COL5A2 | XM_047443251.1 | c.660+5G>A | splice_region_variant, intron_variant | Intron 16 of 58 | XP_047299207.1 | |||
COL5A2 | XM_047443252.1 | c.660+5G>A | splice_region_variant, intron_variant | Intron 15 of 57 | XP_047299208.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.798+5G>A | splice_region_variant, intron_variant | Intron 11 of 53 | 1 | NM_000393.5 | ENSP00000364000.3 | |||
COL5A2 | ENST00000618828.1 | c.168+5G>A | splice_region_variant, intron_variant | Intron 11 of 46 | 5 | ENSP00000482184.1 | ||||
COL5A2 | ENST00000649966.1 | c.*15G>A | downstream_gene_variant | ENSP00000496785.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459006Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2AN XY: 725692
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74334
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
The c.798+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 11 in the COL5A2 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Ehlers-Danlos syndrome, classic type, 2 Uncertain:1
COL5A2 NM_000393.3 (c.798+5G>A): This variant has not been reported in the literature and is not present in large control databases. The identified variant is an intronic variant and no predicted change in the amino acid sequence but may have an unknown effect on splicing. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -
Ehlers-Danlos syndrome, classic type Uncertain:1
COL5A2 NM_000393.3 (c.798+5G>A): This variant has not been reported in the literature and is not present in large control databases. The identified variant is an intronic variant and no predicted change in the amino acid sequence but may have an unknown effect on splicing. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
This sequence change falls in intron 11 of the COL5A2 gene. It does not directly change the encoded amino acid sequence of the COL5A2 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL5A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 487466). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at