rs77804131
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_024809.5(TCTN2):c.898C>T(p.Leu300=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,614,162 control chromosomes in the GnomAD database, including 319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.011 ( 14 hom., cov: 32)
Exomes 𝑓: 0.017 ( 305 hom. )
Consequence
TCTN2
NM_024809.5 synonymous
NM_024809.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0540
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 Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 12-123690539-C-T is Benign according to our data. Variant chr12-123690539-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 126295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123690539-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.054 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0111 (1688/152318) while in subpopulation SAS AF= 0.0306 (148/4830). AF 95% confidence interval is 0.0266. There are 14 homozygotes in gnomad4. There are 833 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 14 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TCTN2 | NM_024809.5 | c.898C>T | p.Leu300= | synonymous_variant | 8/18 | ENST00000303372.7 | NP_079085.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TCTN2 | ENST00000303372.7 | c.898C>T | p.Leu300= | synonymous_variant | 8/18 | 1 | NM_024809.5 | ENSP00000304941 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0111 AC: 1685AN: 152200Hom.: 14 Cov.: 32
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GnomAD3 exomes AF: 0.0143 AC: 3601AN: 251478Hom.: 51 AF XY: 0.0163 AC XY: 2219AN XY: 135920
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GnomAD4 exome AF: 0.0174 AC: 25398AN: 1461844Hom.: 305 Cov.: 32 AF XY: 0.0181 AC XY: 13181AN XY: 727228
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GnomAD4 genome AF: 0.0111 AC: 1688AN: 152318Hom.: 14 Cov.: 32 AF XY: 0.0112 AC XY: 833AN XY: 74478
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 06, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Joubert syndrome 24 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Meckel syndrome, type 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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