rs111574617
Positions:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_024809.5(TCTN2):c.1505+3G>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000722 in 1,600,364 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0036 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00042 ( 3 hom. )
Consequence
TCTN2
NM_024809.5 splice_donor_region, intron
NM_024809.5 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.06464
2
Clinical Significance
Conservation
PhyloP100: 1.02
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 -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 12-123697201-G-C is Benign according to our data. Variant chr12-123697201-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 215939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00357 (544/152300) while in subpopulation AFR AF= 0.0121 (503/41560). AF 95% confidence interval is 0.0112. There are 3 homozygotes in gnomad4. There are 259 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCTN2 | NM_024809.5 | c.1505+3G>C | splice_donor_region_variant, intron_variant | ENST00000303372.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCTN2 | ENST00000303372.7 | c.1505+3G>C | splice_donor_region_variant, intron_variant | 1 | NM_024809.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00357 AC: 544AN: 152182Hom.: 4 Cov.: 33
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GnomAD3 exomes AF: 0.000959 AC: 241AN: 251408Hom.: 1 AF XY: 0.000787 AC XY: 107AN XY: 135878
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GnomAD4 exome AF: 0.000423 AC: 612AN: 1448064Hom.: 3 Cov.: 27 AF XY: 0.000395 AC XY: 285AN XY: 721486
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GnomAD4 genome ? AF: 0.00357 AC: 544AN: 152300Hom.: 3 Cov.: 33 AF XY: 0.00348 AC XY: 259AN XY: 74466
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2022 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 18, 2018 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at