rs863225426
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024809.5(TCTN2):c.1873C>T(p.Gln625Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_024809.5 stop_gained
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCTN2 | NM_024809.5 | c.1873C>T | p.Gln625Ter | stop_gained | 16/18 | ENST00000303372.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCTN2 | ENST00000303372.7 | c.1873C>T | p.Gln625Ter | stop_gained | 16/18 | 1 | NM_024809.5 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727246
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2023 | This sequence change creates a premature translational stop signal (p.Gln625*) in the TCTN2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TCTN2 are known to be pathogenic (PMID: 21565611). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Joubert syndrome (PMID: 21565611). ClinVar contains an entry for this variant (Variation ID: 218100). For these reasons, this variant has been classified as Pathogenic. - |
Joubert syndrome 24 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 13, 2011 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at