chrX-46837098-ACCATGGGCTGCTTCTTCTC-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006915.3(RP2):c.-1_18del variant causes a start lost, 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Consequence
RP2
NM_006915.3 start_lost, 5_prime_UTR
NM_006915.3 start_lost, 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.61
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 12 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-46837098-ACCATGGGCTGCTTCTTCTC-A is Pathogenic according to our data. Variant chrX-46837098-ACCATGGGCTGCTTCTTCTC-A is described in ClinVar as [Pathogenic]. Clinvar id is 2728412.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RP2 | NM_006915.3 | c.-1_18del | start_lost, 5_prime_UTR_variant | 1/5 | ENST00000218340.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RP2 | ENST00000218340.4 | c.-1_18del | start_lost, 5_prime_UTR_variant | 1/5 | 1 | NM_006915.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 26, 2023 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the RP2 protein in which other variant(s) (p.Ser6del) have been determined to be pathogenic (PMID: 9697692, 10942419, 17724181, 28209709; 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. This variant has not been reported in the literature in individuals affected with RP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the RP2 mRNA. The next in-frame methionine is located at codon 41. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.