rs761238771
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001142800.2(EYS):c.4350_4356delTATAGCT(p.Ile1451ProfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000948 in 1,551,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001142800.2 frameshift
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 rank | MANE | Protein | UniProt |
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EYS | NM_001142800.2 | c.4350_4356delTATAGCT | p.Ile1451ProfsTer3 | frameshift_variant | Exon 26 of 43 | ENST00000503581.6 | NP_001136272.1 | |
EYS | NM_001292009.2 | c.4350_4356delTATAGCT | p.Ile1451ProfsTer3 | frameshift_variant | Exon 26 of 44 | NP_001278938.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EYS | ENST00000503581.6 | c.4350_4356delTATAGCT | p.Ile1451ProfsTer3 | frameshift_variant | Exon 26 of 43 | 5 | NM_001142800.2 | ENSP00000424243.1 | ||
EYS | ENST00000370621.7 | c.4350_4356delTATAGCT | p.Ile1451ProfsTer3 | frameshift_variant | Exon 26 of 44 | 1 | ENSP00000359655.3 |
Frequencies
GnomAD3 genomes AF: 0.0000987 AC: 15AN: 152020Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000783 AC: 12AN: 153194Hom.: 0 AF XY: 0.0000615 AC XY: 5AN XY: 81256
GnomAD4 exome AF: 0.0000943 AC: 132AN: 1399160Hom.: 0 AF XY: 0.0000754 AC XY: 52AN XY: 690088
GnomAD4 genome AF: 0.0000987 AC: 15AN: 152020Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7AN XY: 74238
ClinVar
Submissions by phenotype
not provided Pathogenic:6
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Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25491159, 32531858, 21217109, 31074760, 30718709, 32037395, 20537394) -
This sequence change creates a premature translational stop signal (p.Ile1451Profs*3) in the EYS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EYS are known to be pathogenic (PMID: 18836446, 20333770). This variant is present in population databases (rs761238771, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 20537394, 24265693, 31074760). ClinVar contains an entry for this variant (Variation ID: 195936). For these reasons, this variant has been classified as Pathogenic. -
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Retinitis pigmentosa 25 Pathogenic:6
The EYS c.4350_4356del variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PP1. Based on this evidence we have classified this variant as Pathogenic. -
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This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP5. -
Retinitis pigmentosa Pathogenic:4
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The p.Ile1451ProfsTer3 variant in EYS was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PM2. Based on this evidence we have classified this variant as Likely Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab. -
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Retinal dystrophy Pathogenic:2
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at