rs121918561
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_000322.5(PRPH2):c.356_358del(p.Cys119del) variant causes a inframe deletion 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 Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
PRPH2
NM_000322.5 inframe_deletion
NM_000322.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.54
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_000322.5. Strenght limited to Supporting due to length of the change: 1aa.
PP5
?
Variant 6-42721976-AAGC-A is Pathogenic according to our data. Variant chr6-42721976-AAGC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 13162.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-42721976-AAGC-A is described in Lovd as [Likely_pathogenic]. Variant chr6-42721976-AAGC-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPH2 | NM_000322.5 | c.356_358del | p.Cys119del | inframe_deletion | 1/3 | ENST00000230381.7 | |
PRPH2 | XR_007059288.1 | n.619_621del | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPH2 | ENST00000230381.7 | c.356_358del | p.Cys119del | inframe_deletion | 1/3 | 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/Likely pathogenic
Submissions summary: Pathogenic:2Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Pathogenic:1Other:1
Likely pathogenic, no assertion criteria provided | curation | Leiden Open Variation Database | Apr 06, 2021 | Curator: Global Variome, with Curator vacancy. Submitter to LOVD: Manon Peeters. - |
not provided, no classification provided | literature only | Retina International | - | - - |
Retinitis pigmentosa 7 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 1993 | - - |
Computational scores
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Calibrated prediction
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Splicing
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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