12-123671310-T-TG
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_024809.5(TCTN2):c.76dupG(p.Asp26fs) 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 (★).
Frequency
Genomes: not found (cov: 32)
Consequence
TCTN2
NM_024809.5 frameshift
NM_024809.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.591
Genes affected
TCTN2 (HGNC:25774): (tectonic family member 2) This gene encodes a type I membrane protein that belongs to the tectonic family. Studies in mice suggest that this protein may be involved in hedgehog signaling, and essential for ciliogenesis. Mutations in this gene are associated with Meckel syndrome type 8. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-123671310-T-TG is Pathogenic according to our data. Variant chr12-123671310-T-TG is described in ClinVar as [Pathogenic]. Clinvar id is 217700.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TCTN2 | NM_024809.5 | c.76dupG | p.Asp26fs | frameshift_variant | 1/18 | ENST00000303372.7 | NP_079085.2 | |
| TCTN2 | NM_001143850.3 | c.76dupG | p.Asp26fs | frameshift_variant | 1/18 | NP_001137322.1 | ||
| TCTN2 | NM_001410989.1 | c.76dupG | p.Asp26fs | frameshift_variant | 1/17 | NP_001397918.1 | ||
| TCTN2 | XM_017019974.2 | c.76dupG | p.Asp26fs | frameshift_variant | 1/17 | XP_016875463.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Joubert syndrome 24 Pathogenic:1
| Pathogenic, no assertion criteria provided | literature only | OMIM | May 13, 2011 | - - |
Familial aplasia of the vermis Pathogenic:1
| Pathogenic, criteria provided, single submitter | research | UW Hindbrain Malformation Research Program, University of Washington | Feb 23, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at