rs797046040
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024809.5(TCTN2):c.134dup(p.Val46GlyfsTer32) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000205 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
TCTN2
NM_024809.5 frameshift
NM_024809.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.05
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 12-123671557-C-CT is Pathogenic according to our data. Variant chr12-123671557-C-CT is described in ClinVar as [Pathogenic]. Clinvar id is 212387.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCTN2 | NM_024809.5 | c.134dup | p.Val46GlyfsTer32 | frameshift_variant | 2/18 | ENST00000303372.7 | |
TCTN2 | NM_001143850.3 | c.134dup | p.Val46GlyfsTer32 | frameshift_variant | 2/18 | ||
TCTN2 | NM_001410989.1 | c.134dup | p.Val46GlyfsTer32 | frameshift_variant | 2/17 | ||
TCTN2 | XM_017019974.2 | c.134dup | p.Val46GlyfsTer32 | frameshift_variant | 2/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCTN2 | ENST00000303372.7 | c.134dup | p.Val46GlyfsTer32 | frameshift_variant | 2/18 | 1 | NM_024809.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251366Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135876
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461776Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727210
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Meckel syndrome, type 8 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 19, 2015 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at