rs786205652
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001142800.2(EYS):βc.179delβ(p.Leu60TrpfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,826 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: 6.8e-7 ( 0 hom. )
Consequence
EYS
NM_001142800.2 frameshift
NM_001142800.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.428
Genes affected
EYS (HGNC:21555): (eyes shut homolog) The product of this gene contains multiple epidermal growth factor (EGF)-like and LamG domains. The protein is expressed in the photoreceptor layer of the retina, and the gene is mutated in autosomal recessive retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]
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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 6-65495231-CA-C is Pathogenic according to our data. Variant chr6-65495231-CA-C is described in ClinVar as [Pathogenic]. Clinvar id is 191332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-65495231-CA-C is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EYS | NM_001142800.2 | c.179del | p.Leu60TrpfsTer3 | frameshift_variant | 4/43 | ENST00000503581.6 | NP_001136272.1 | |
EYS | NM_001292009.2 | c.179del | p.Leu60TrpfsTer3 | frameshift_variant | 4/44 | NP_001278938.1 | ||
EYS | NM_001142801.2 | c.179del | p.Leu60TrpfsTer3 | frameshift_variant | 4/12 | NP_001136273.1 | ||
EYS | NM_198283.2 | c.179del | p.Leu60TrpfsTer3 | frameshift_variant | 3/10 | NP_938024.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EYS | ENST00000503581.6 | c.179del | p.Leu60TrpfsTer3 | frameshift_variant | 4/43 | 5 | NM_001142800.2 | ENSP00000424243 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461826Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727212
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal recessive retinitis pigmentosa Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | Faculty of Health Sciences, Beirut Arab University | Sep 10, 2015 | - - |
not provided Pathogenic:1
Likely pathogenic, flagged submission | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | - | - - |
Retinitis pigmentosa 25 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Apr 04, 2024 | - - |
Retinal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at