Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: RPGR vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001034853.2(RPGR):c.2405_2406del (p.Glu802fs)

CA266215

91389 (ClinVar)

Gene: RPGR
Condition: RPGR-related retinopathy
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 8f3393bf-e670-4597-80c5-8b3bdbec5e18
Approved on: 2025-05-20
Published on: 2025-05-21

HGVS expressions

NM_001034853.2:c.2405_2406del
NM_001034853.2(RPGR):c.2405_2406del (p.Glu802fs)
NC_000023.11:g.38286595_38286596del
CM000685.2:g.38286595_38286596del
NC_000023.10:g.38145848_38145849del
CM000685.1:g.38145848_38145849del
NC_000023.9:g.38030792_38030793del
NG_009553.1:g.45942_45943del
ENST00000494707.6:c.953+1271_953+1272del
ENST00000642170.1:n.1826+4365_1826+4366del
ENST00000642395.2:c.1905+500_1905+501del
ENST00000642739.1:c.1572+4365_1572+4366del
ENST00000644238.1:c.1386+4365_1386+4366del
ENST00000644337.1:c.1719+500_1719+501del
ENST00000645032.1:c.2405_2406del
ENST00000645124.1:c.*101+500_*101+501del
ENST00000646020.1:c.*594+500_*594+501del
ENST00000318842.11:c.1905+500_1905+501del
ENST00000339363.7:c.2520+500_2520+501del
ENST00000378505.6:c.2405_2406del
ENST00000465127.1:c.172-379526_172-379525del
ENST00000474584.5:c.*37+4365_*37+4366del
ENST00000482855.5:c.1905+500_1905+501del
ENST00000494707.5:c.139+4365_139+4366del
NM_000328.2:c.1905+500_1905+501del
NM_001034853.1:c.2405_2406del
NM_001367245.1:c.1902+500_1902+501del
NM_001367246.1:c.1719+500_1719+501del
NM_001367247.1:c.1572+4365_1572+4366del
NM_001367248.1:c.1602+4365_1602+4366del
NM_001367249.1:c.1569+4365_1569+4366del
NM_001367250.1:c.1569+4365_1569+4366del
NM_001367251.1:c.1386+4365_1386+4366del
NR_159803.1:n.2263+500_2263+501del
NR_159804.1:n.1648+4365_1648+4366del
NR_159805.1:n.1714+4365_1714+4366del
NR_159806.1:n.1866+500_1866+501del
NR_159807.1:n.1622+4365_1622+4366del
NR_159808.1:n.1826+4365_1826+4366del
NM_000328.3:c.1905+500_1905+501del
More

Pathogenic

Met criteria codes 5
PS4 PP4_Moderate PVS1 PM2_Supporting PP1_Strong
Not Met criteria codes 16
PS2 PS3 PP3 PP2 PM6 PM3 PM1 PM4 BS3 BS1 BP5 BP7 BP2 BP4 BP1 BA1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
X-linked Inherited Retinal Disease VCEP
NM_001034853.2(RPGR):c.2405_2406del (p.Glu802GlyfsTer?) is a frameshift variant that introduces a premature stop codon into exon 15 of 15 before amino acid 1132, which is predicted not to trigger nonsense-mediated decay but rather to disrupt a critical C-terminal region required for proper glutamylation of RPGR (PVS1, PMID: 36445968). This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_supporting). This variant has been reported in at least 6 apparently unrelated probands meeting the PS4 requirement of some functional vision impairment in affected males by age 30 years and/or decreased or absent cone and/or rod electroretinogram responses (PMID: 34745198, 29453956, PS4). The variant has been reported to segregate with retinal dystrophy through at least 4 affected meioses from at least 2 families (PP1_strong, PMID: 34745198, 21857984). In summary, this variant is classified as pathogenic for RPGR-related retinopathy based on the ClinGen X-linked Inherited Retinal Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPGR Version 1.0.0; PVS1, PS4, PM2_supporting, and PP1_strong. (date of approval 05/16/2025).
Met criteria codes
PS4
This variant has been reported in at least 6 apparently unrelated probands meeting the PS4 requirement of some functional vision impairment in affected males by age 30, with decreased or absent cone and/or rod ERG responses (PMID: 34745198, 29453956, PS4).
PP4_Moderate
At least one proband harboring this variant exhibits a phenotype including WES (2 pts), X-linked inheritance (2 pts), early onset (1 pt), Night blindness (0.5 pts), visual field constriction (0.5 pts), decreased visual acuity (0.5 pts), nystagmus, Myopia (0.5 pts), Bone spicules in the periphery (0.5 pts), optic disc pallor (0.5 pts), which together are highly specific for RPGR-related recessive retinopathy (8 points, PMID: 25544989, PP4_Moderate).
PVS1
This is a frameshift variant that introduces a premature stop codon into exon 15 of 15 before amino acid 1132, that is predicted not to trigger nonsense-mediated decay but rather to disrupt a critical C-terminal region required for proper glutamylation of RPGR (PVS1, PMID: 36445968).
PM2_Supporting
This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_Supporting).
PP1_Strong
The variant has been reported to segregate with retinal dystrophy through at least 4 affected meioses from at least 2 families (PP1_Strong, PMID: 34745198, 21857984, 25544989).
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.