8-54620970-AGT-A
Position:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006269.2(RP1):c.6_7del(p.Ser2ArgfsTer16) variant causes a frameshift change. 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
RP1
NM_006269.2 frameshift
NM_006269.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.22
Genes affected
RP1 (HGNC:10263): (RP1 axonemal microtubule associated) This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two doublecortin domains, which bind microtubules and regulate microtubule polymerization. The encoded protein is a photoreceptor microtubule-associated protein and is required for correct stacking of outer segment disc. This protein and the RP1L1 protein, another retinal-specific protein, play essential and synergistic roles in affecting photosensitivity and outer segment morphogenesis of rod photoreceptors. Because of its response to in vivo retinal oxygen levels, this protein was initially named ORP1 (oxygen-regulated protein-1). This protein was subsequently designated RP1 (retinitis pigmentosa 1) when it was found that mutations in this gene cause autosomal dominant retinitis pigmentosa. Mutations in this gene also cause autosomal recessive retinitis pigmentosa. Transcript variants resulted from an alternative promoter and alternative splicings have been found, which overlap the current reference sequence and has several exons upstream and downstream of the current reference sequence. However, the biological validity and full-length nature of some variants cannot be determined at this time.[provided by RefSeq, Sep 2010]
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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 located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 324 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 8-54620970-AGT-A is Pathogenic according to our data. Variant chr8-54620970-AGT-A is described in ClinVar as [Pathogenic]. Clinvar id is 2500819.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-54620970-AGT-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RP1 | NM_006269.2 | c.6_7del | p.Ser2ArgfsTer16 | frameshift_variant | 2/4 | ENST00000220676.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RP1 | ENST00000220676.2 | c.6_7del | p.Ser2ArgfsTer16 | frameshift_variant | 2/4 | 1 | NM_006269.2 | ||
RP1 | ENST00000636932.1 | c.6_7del | p.Ser2ArgfsTer16 | frameshift_variant | 2/23 | 5 | |||
RP1 | ENST00000637698.1 | c.6_7del | p.Ser2ArgfsTer16 | frameshift_variant | 2/29 | 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:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Retinitis pigmentosa 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Pangenia Genomics, Pangenia Inc. | Mar 14, 2022 | The RP1, c.6_7delTG (p.Ser2Argfs*16) variant is a frameshift variant in exon 2 of RP1 gene, resulting in a premature translation stop signal in the mRNA predicted to undergo nonsense mediated decay, creating a null variant of the RP1 gene. This variant is absent from controls in population database. There is presence of co-segregation with disease in multiple affected family members. This variant is detected in trans with a likely-pathogenic variant [RP1, c.4941dupT (p.Pro1648Serfs*13)]. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.