chr2-178692008-TGGC-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_001267550.2(TTN):c.31762+5_31762+7del variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,609,428 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001267550.2 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.31762+5_31762+7del | splice_donor_5th_base_variant, intron_variant | ENST00000589042.5 | |||
LOC124907912 | XR_007087321.1 | n.3873_3875del | non_coding_transcript_exon_variant | 1/2 | |||
LOC124906100 | XR_007087318.1 | n.2186-21744_2186-21742del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.31762+5_31762+7del | splice_donor_5th_base_variant, intron_variant | 5 | NM_001267550.2 | P1 | |||
TTN-AS1 | ENST00000659121.1 | n.503-42494_503-42492del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000146 AC: 36AN: 246816Hom.: 0 AF XY: 0.000134 AC XY: 18AN XY: 133922
GnomAD4 exome AF: 0.000200 AC: 292AN: 1457162Hom.: 0 AF XY: 0.000182 AC XY: 132AN XY: 724720
GnomAD4 genome AF: 0.000118 AC: 18AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74450
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:4
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 09, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | TTN: BP4 - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 14, 2017 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 16, 2018 | c.28030+5_28030+7delGCC in intron 118 of TTN: This variant is not expected to ha ve clinical significance because it has been identified in 0.04% (10/25696) of F innish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.bro adinstitute.org; dbSNP rs397517538). In addition, this variant is located in the 5' splice region and computational tools do not suggest an impact to splicing. ACMG/AMP Criteria applied: BS1; BP4. - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 20, 2015 | 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. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at