Variant: NM_001034853.2(RPGR):c.1512_1513del (p.Ile505fs)

Version: 1.0
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CA226367

98746 (ClinVar)

Gene: RPGR (HGNC:6103)

Condition: RPGR-related retinopathy

Inheritance Mode: X-linked inheritance

UUID: 14b306f2-b073-4f92-913c-974dad624a92

Approved on: 2025-08-01

Published on: 2025-08-02

HGVS expressions

NM_001034853.2:c.1512_1513del
NM_001034853.2(RPGR):c.1512_1513del (p.Ile505fs)
NC_000023.11:g.38291023_38291024del
CM000685.2:g.38291023_38291024del
NC_000023.10:g.38150276_38150277del
CM000685.1:g.38150276_38150277del
NC_000023.9:g.38035220_38035221del
NG_009553.1:g.41517_41518del
ENST00000494707.6:c.716_717del
ENST00000642170.1:n.1766_1767del
ENST00000642395.2:c.1512_1513del
ENST00000642739.1:c.1512_1513del
ENST00000644238.1:c.1326_1327del
ENST00000644337.1:c.1326_1327del
ENST00000645032.1:c.1512_1513del
ENST00000645124.1:c.1512_1513del
ENST00000646020.1:c.*205_*206del
ENST00000318842.11:c.1512_1513del
ENST00000339363.7:c.1512_1513del
ENST00000378505.6:c.1512_1513del
ENST00000465127.1:c.172-375098_172-375097del
ENST00000474584.5:c.1420_1421del
ENST00000482855.5:c.1512_1513del
ENST00000494707.5:c.79_80del
NM_000328.2:c.1512_1513del
NM_001034853.1:c.1512_1513del
NM_001367245.1:c.1509_1510del
NM_001367246.1:c.1326_1327del
NM_001367247.1:c.1512_1513del
NM_001367248.1:c.1542_1543del
NM_001367249.1:c.1509_1510del
NM_001367250.1:c.1509_1510del
NM_001367251.1:c.1326_1327del
NR_159803.1:n.1874_1875del
NR_159804.1:n.1588_1589del
NR_159805.1:n.1654_1655del
NR_159806.1:n.1654_1655del
NR_159807.1:n.1562_1563del
NR_159808.1:n.1766_1767del
NM_000328.3:c.1512_1513del

Pathogenic

• Met criteria codes: PVS1 PM2_Supporting PP4 PP1_Moderate

Expert Panel

X-linked Inherited Retinal Disease VCEP

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

Evidence submitted by expert panel

X-linked Inherited Retinal Disease VCEP

NM_001034853.2(RPGR):c.1512_1513del (p.Ile505HisfsTer7) is a 2-bp deletion variant in exon 13 of 15, which results in a frameshift and premature stop codon after 7 amino acids and is predicted to trigger nonsense-mediated decay (PVS1). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). The variant has been reported to segregate with retinal dystrophy through at least 3 affected meioses from 1 family. (PP1_Moderate; PMID: 9488274). At least one proband harboring this variant exhibits a phenotype including a family history consistent with X-linked inheritance (2 pts), childhood-onset (1 pt), mild myopia, pale optic discs (0.5 pts), visual field constriction (0.5 pts), and reduced visual acuity (0.5 pts), which together are specific for RPGR-related retinopathy (4.5 points, PMID: 9488274, PP4). 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, PM2_Supporting, PP1_Moderate, and PP4. (date of approval 05/16/2025).

Met criteria codes

• PVS1: This is a frameshift variant that introduces a premature stop codon between amino acids 1-1132 that is predicted to either trigger nonsense-mediated decay or to disrupt a critical C-terminal region required for proper glutamylation of RPGR (PVS1, PMID: 36445968).
• PM2_Supporting: This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
• PP4: At least one proband harboring this variant exhibits a phenotype including a family history consistent with X-linked inheritance (2 pts), childhood-onset (1 pt), mild myopia, pale optic discs (0.5 pts), visual field constriction (0.5 pts), and reduced visual acuity (0.5 pts), which together are specific for RPGR-related retinopathy (4.5 points, PMID: 9488274, PP4).
• PP1_Moderate: The variant has been reported to segregate with retinal dystrophy through at least 3 affected meioses from 1 family. (PP1_Moderate; PMID: 9488274).