rs777850798
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4BS1BS2
The NM_001034853.2(RPGR):βc.2447_2461delβ(p.Gly816_Glu820del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 896,827 control chromosomes in the GnomAD database, including 7 homozygotes. There are 907 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (β β ).
Frequency
Genomes: π 0.0018 ( 0 hom., 0 hem., cov: 4)
Exomes π: 0.0035 ( 7 hom. 907 hem. )
Consequence
RPGR
NM_001034853.2 inframe_deletion
NM_001034853.2 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.59
Genes affected
RPGR (HGNC:10295): (retinitis pigmentosa GTPase regulator) This gene encodes a protein with a series of six RCC1-like domains (RLDs), characteristic of the highly conserved guanine nucleotide exchange factors. The encoded protein is found in the Golgi body and interacts with RPGRIP1. This protein localizes to the outer segment of rod photoreceptors and is essential for their viability. Mutations in this gene have been associated with X-linked retinitis pigmentosa (XLRP). Multiple alternatively spliced transcript variants that encode different isoforms of this gene have been reported, but the full-length natures of only some have been determined. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_001034853.2.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00354 (3064/864447) while in subpopulation NFE AF= 0.0041 (2835/691275). AF 95% confidence interval is 0.00397. There are 7 homozygotes in gnomad4_exome. There are 907 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 7 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPGR | NM_001034853.2 | c.2447_2461del | p.Gly816_Glu820del | inframe_deletion | 15/15 | ENST00000645032.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPGR | ENST00000645032.1 | c.2447_2461del | p.Gly816_Glu820del | inframe_deletion | 15/15 | NM_001034853.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00179 AC: 58AN: 32387Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0AN XY: 1997
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GnomAD3 exomes AF: 0.00114 AC: 105AN: 91821Hom.: 0 AF XY: 0.000651 AC XY: 16AN XY: 24565
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GnomAD4 exome AF: 0.00354 AC: 3064AN: 864447Hom.: 7 AF XY: 0.00347 AC XY: 907AN XY: 261387
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ClinVar
Significance: Likely benign
Submissions summary: Pathogenic:1Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 30, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | RPGR: BS2 - |
X-linked cone-rod dystrophy 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2002 | - - |
Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at