rs398123576
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001142800.2(EYS):c.8408_8409insA(p.Asn2803LysfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 1,399,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. N2803N) has been classified as Likely benign.
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EYS | NM_001142800.2 | c.8408_8409insA | p.Asn2803LysfsTer9 | frameshift_variant | 43/43 | ENST00000503581.6 | |
PHF3 | NM_001370348.2 | c.*7917dup | 3_prime_UTR_variant | 16/16 | ENST00000262043.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EYS | ENST00000503581.6 | c.8408_8409insA | p.Asn2803LysfsTer9 | frameshift_variant | 43/43 | 5 | NM_001142800.2 | A2 | |
EYS | ENST00000370621.7 | c.8471_8472insA | p.Asn2824LysfsTer9 | frameshift_variant | 44/44 | 1 | P2 | ||
PHF3 | ENST00000262043.8 | c.*7917dup | 3_prime_UTR_variant | 16/16 | 5 | NM_001370348.2 | P1 | ||
PHF3 | ENST00000505138.1 | c.363+10263dup | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000191 AC: 3AN: 157218Hom.: 0 AF XY: 0.0000120 AC XY: 1AN XY: 83090
GnomAD4 exome AF: 0.0000336 AC: 47AN: 1399074Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 19AN XY: 690050
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 06, 2023 | This sequence change creates a premature translational stop signal (p.Asn2803Lysfs*9) in the EYS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 342 amino acid(s) of the EYS protein. This variant is present in population databases (rs398123576, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with retinitis pigmentosa (PMID: 23591405, 28704921; Invitae). ClinVar contains an entry for this variant (Variation ID: 93622). This variant disrupts a region of the EYS protein in which other variant(s) (p.Val3096Leufs*28) have been determined to be pathogenic (PMID: 24474277, 26261414, 29550188). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 10, 2013 | - - |
Retinitis pigmentosa 25 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 10, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Retinal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Dec 17, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at