rs121918355
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000428.3(LTBP2):c.895C>T(p.Arg299Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,444,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000428.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LTBP2 | NM_000428.3 | c.895C>T | p.Arg299Ter | stop_gained | 4/36 | ENST00000261978.9 | |
LOC124903346 | XR_007064265.1 | n.99+3216G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LTBP2 | ENST00000261978.9 | c.895C>T | p.Arg299Ter | stop_gained | 4/36 | 1 | NM_000428.3 | P1 | |
ENST00000554552.1 | n.233+3216G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000208 AC: 5AN: 240674Hom.: 0 AF XY: 0.0000231 AC XY: 3AN XY: 130096
GnomAD4 exome AF: 0.0000104 AC: 15AN: 1444814Hom.: 0 Cov.: 32 AF XY: 0.0000112 AC XY: 8AN XY: 716232
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 7554). This premature translational stop signal has been observed in individuals with clinical features of LTBP2-related conditions (PMID: 19361779, 21081970; Invitae). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs121918355, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg299*) in the LTBP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LTBP2 are known to be pathogenic (PMID: 19361779, 19656777, 22025892). - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2020 | - - |
Glaucoma 3, primary congenital, D Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2011 | - - |
Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory of Medical Genetics, National & Kapodistrian University of Athens | Mar 17, 2023 | PVS1, PM2, PP5 - |
Microspherophakia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2011 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at