12-47973409-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_001844.5(COL2A1):c.4462T>C(p.Ter1488Glnext*?) variant causes a stop lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001844.5 stop_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL2A1 | ENST00000380518.8 | c.4462T>C | p.Ter1488Glnext*? | stop_lost | Exon 54 of 54 | 1 | NM_001844.5 | ENSP00000369889.3 | ||
COL2A1 | ENST00000337299.7 | c.4255T>C | p.Ter1419Glnext*? | stop_lost, splice_region_variant | Exon 53 of 53 | 1 | ENSP00000338213.6 | |||
COL2A1 | ENST00000493991.5 | n.3548T>C | non_coding_transcript_exon_variant | Exon 37 of 37 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
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. This protein extension has been observed in individuals with autosomal dominant spondyloepiphyseal dysplasia congenita (PMID: 32071555; Invitae). This sequence change disrupts the translational stop signal of the COL2A1 mRNA. It is expected to extend the length of the COL2A1 protein by 34 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.