chr12-123694981-C-G
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The NM_024809.5(TCTN2):c.1234+5C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_024809.5 splice_region, intron
Scores
Clinical Significance
Conservation
Publications
- Joubert syndrome 24Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- Joubert syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Meckel syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152072Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00000400 AC: 1AN: 249952 AF XY: 0.00000737 show subpopulations
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460902Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726752 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000112 AC: 17AN: 152190Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74398 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Uncertain:1
- -
Meckel-Gruber syndrome;C0431399:Joubert syndrome Uncertain:1
This sequence change falls in intron 10 of the TCTN2 gene. It does not directly change the encoded amino acid sequence of the TCTN2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs201382614, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TCTN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 408315). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at