rs878853382
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001122769.3(LCA5):βc.633_639delβ(p.Glu211AspfsTer13) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000137 in 1,461,524 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes π: 0.0000014 ( 0 hom. )
Consequence
LCA5
NM_001122769.3 frameshift
NM_001122769.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.51
Genes affected
LCA5 (HGNC:31923): (lebercilin LCA5) This gene encodes a protein that is thought to be involved in centrosomal or ciliary functions. Mutations in this gene cause Leber congenital amaurosis type V. Alternatively spliced transcript variants are described. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-79513292-GTCTAGCT-G is Pathogenic according to our data. Variant chr6-79513292-GTCTAGCT-G is described in ClinVar as [Pathogenic]. Clinvar id is 236493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-79513292-GTCTAGCT-G is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LCA5 | NM_001122769.3 | c.633_639del | p.Glu211AspfsTer13 | frameshift_variant | 3/8 | ENST00000369846.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LCA5 | ENST00000369846.9 | c.633_639del | p.Glu211AspfsTer13 | frameshift_variant | 3/8 | 1 | NM_001122769.3 | P1 | |
LCA5 | ENST00000392959.5 | c.633_639del | p.Glu211AspfsTer13 | frameshift_variant | 4/9 | 1 | P1 | ||
ENST00000652956.1 | n.470-13680_470-13674del | intron_variant, non_coding_transcript_variant | |||||||
LCA5 | ENST00000467898.3 | c.633_639del | p.Glu211AspfsTer13 | frameshift_variant | 3/7 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461524Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727078
GnomAD4 exome
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2
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1461524
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727078
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Retinal dystrophy Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Oct 24, 2018 | - - |
Likely pathogenic, no assertion criteria provided | clinical testing | Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals | - | - - |
Pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2018 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at