21-45504504-GC-GCC
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001379500.1(COL18A1):c.2823dupC(p.Gly942ArgfsTer145) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001379500.1 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL18A1 | NM_001379500.1 | c.2823dupC | p.Gly942ArgfsTer145 | frameshift_variant | Exon 34 of 42 | ENST00000651438.1 | NP_001366429.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 29
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 29
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Identified in siblings with Knobloch syndrome in published literature, also known as c.3363_3364insC (PMID: 14695535); Frameshift 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: 14695535) -
Knobloch syndrome Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at