5-83537002-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_004385.5(VCAN):c.4004-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_004385.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VCAN | NM_004385.5 | c.4004-5T>C | splice_region_variant, intron_variant | Intron 7 of 14 | ENST00000265077.8 | NP_004376.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 29
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:2
This sequence change falls in intron 7 of the VCAN gene. It does not directly change the encoded amino acid sequence of the VCAN protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Wagner syndrome (PMID: 16877430). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 21407). Studies have shown that this variant is associated with altered splicing resulting in multiple RNA products (PMID: 16877430). For these reasons, this variant has been classified as Pathogenic. -
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Wagner syndrome Pathogenic:1Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at