rs786204788
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The ENST00000303372.7(TCTN2):c.1877T>A(p.Leu626Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L626L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000303372.7 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TCTN2 | NM_024809.5 | c.1877T>A | p.Leu626Ter | stop_gained | 16/18 | ENST00000303372.7 | NP_079085.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TCTN2 | ENST00000303372.7 | c.1877T>A | p.Leu626Ter | stop_gained | 16/18 | 1 | NM_024809.5 | ENSP00000304941 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Familial aplasia of the vermis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 20, 2014 | The Leu626X variant in TCTN2 has not been previously identified in individuals with Joubert syndrome or in large population studies. However, this nonsense variant leads to a premature termination codon at position 626, which is predicted to lead to a truncated or absent protein. Loss-of-function variants in the TCTN2 gene, including another nonsense variant in this exon, have been previously reported in individuals with autosomal recessive ciliopathies including Joubert syndrome (Sang 2011) and Meckel-Gruber syndrome (Shaheen 2011). In summary, this variant meets our criteria to be classified as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at