rs1556313474
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_006915.3(RP2):c.43del(p.Ser15ArgfsTer31) variant causes a frameshift change involving the alteration of a non-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: 23)
Exomes 𝑓: 9.5e-7 ( 0 hom. 1 hem. )
Failed GnomAD Quality Control
Consequence
RP2
NM_006915.3 frameshift
NM_006915.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0460
Genes affected
RP2 (HGNC:10274): (RP2 activator of ARL3 GTPase) The RP2 locus has been implicated as one cause of X-linked retinitis pigmentosa. The predicted gene product shows homology with human cofactor C, a protein involved in the ultimate step of beta-tubulin folding. Progressive retinal degeneration may therefore be due to the accumulation of incorrectly-folded photoreceptor or neuron-specific tubulin isoforms followed by progressive cell death [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 61 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-46837142-GT-G is Pathogenic according to our data. Variant chrX-46837142-GT-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 437945.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-46837142-GT-G is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RP2 | NM_006915.3 | c.43del | p.Ser15ArgfsTer31 | frameshift_variant | 1/5 | ENST00000218340.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RP2 | ENST00000218340.4 | c.43del | p.Ser15ArgfsTer31 | frameshift_variant | 1/5 | 1 | NM_006915.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.46e-7 AC: 1AN: 1057079Hom.: 0 Cov.: 30 AF XY: 0.00000289 AC XY: 1AN XY: 345719
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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1
AN:
1057079
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Cov.:
30
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1
AN XY:
345719
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Abnormality of the eye Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | Undetermined rare ocular disorder with frequency of less than eight patients - |
Computational scores
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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