rs1554268546
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000322.5(PRPH2):c.860_867del(p.Gln287ProfsTer11) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
PRPH2
NM_000322.5 frameshift
NM_000322.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.96
Genes affected
PRPH2 (HGNC:9942): (peripherin 2) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein found in the outer segment of both rod and cone photoreceptor cells. It may function as an adhesion molecule involved in stabilization and compaction of outer segment disks or in the maintenance of the curvature of the rim. This protein is essential for disk morphogenesis. Defects in this gene are associated with both central and peripheral retinal degenerations. Some of the various phenotypically different disorders are autosomal dominant retinitis pigmentosa, progressive macular degeneration, macular dystrophy and retinitis pigmentosa digenic. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 36 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-42698468-GCGACGTCT-G is Pathogenic according to our data. Variant chr6-42698468-GCGACGTCT-G is described in ClinVar as [Pathogenic]. Clinvar id is 437968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-42698468-GCGACGTCT-G is described in Lovd as [Pathogenic]. Variant chr6-42698468-GCGACGTCT-G is described in Lovd as [Pathogenic]. Variant chr6-42698468-GCGACGTCT-G is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPH2 | NM_000322.5 | c.860_867del | p.Gln287ProfsTer11 | frameshift_variant | 3/3 | ENST00000230381.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPH2 | ENST00000230381.7 | c.860_867del | p.Gln287ProfsTer11 | frameshift_variant | 3/3 | 1 | NM_000322.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, no assertion criteria provided | curation | Leiden Open Variation Database | Jan 27, 2021 | Curator: Global Variome, with Curator vacancy. Submitter to LOVD: LOVD. - |
PRPH2-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | This sequence change creates a premature translational stop signal (p.Gln287Profs*11) in the PRPH2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 60 amino acid(s) of the PRPH2 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of PRPH2-related conditions (PMID: 28041643). ClinVar contains an entry for this variant (Variation ID: 437968). This variant disrupts a region of the PRPH2 protein in which other variant(s) (p.Val332Glu) have been determined to be pathogenic (PMID: 30718709, 32531846; Invitae). 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. - |
Retinitis pigmentosa Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at