Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001034853.2:c.122C>G

CA412745793

Gene: RPGR (HGNC:6103)

Condition: RPGR-related retinopathy (MONDO:0100437)

Inheritance Mode: X-linked inheritance

UUID: 9825e969-0cc1-4750-a89a-659f26690b3b

Approved on: 2025-08-01

Published on: 2025-08-01

HGVS expressions

NM_001034853.2:c.122C>G

NC_000023.11:g.38323431G>C

CM000685.2:g.38323431G>C

NC_000023.10:g.38182684G>C

CM000685.1:g.38182684G>C

NC_000023.9:g.38067628G>C

NG_009553.1:g.9105C>G

ENST00000642170.1:n.532C>G

ENST00000642373.1:c.122C>G

ENST00000642395.2:c.122C>G

ENST00000642558.1:c.122C>G

ENST00000642739.1:c.122C>G

ENST00000644238.1:c.122C>G

ENST00000644337.1:c.122C>G

ENST00000645032.1:c.122C>G

ENST00000645124.1:c.122C>G

ENST00000646020.1:c.122C>G

ENST00000647261.1:c.122C>G

ENST00000318842.11:c.122C>G

ENST00000339363.7:c.122C>G

ENST00000378505.6:c.122C>G

ENST00000465127.1:c.172-342690G>C

ENST00000474584.5:c.122C>G

ENST00000482855.5:c.122C>G

NM_000328.2:c.122C>G

NM_001034853.1:c.122C>G

NM_001367245.1:c.122C>G

NM_001367246.1:c.122C>G

NM_001367247.1:c.122C>G

NM_001367248.1:c.152C>G

NM_001367249.1:c.122C>G

NM_001367250.1:c.122C>G

NM_001367251.1:c.122C>G

NR_159803.1:n.264C>G

NR_159804.1:n.264C>G

NR_159805.1:n.264C>G

NR_159806.1:n.264C>G

NR_159807.1:n.264C>G

NR_159808.1:n.532C>G

NM_000328.3:c.122C>G

Likely Pathogenic

PM2_Supporting PVS1

PP1 PS4

Evidence Links 0

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

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.122C>G (p.Ser41Ter) is a nonsense variant that substitutes a premature stop codon for amino acid 41 in exon 2 of 15 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 1 affected meiosis from 1 family, but details are not sufficient to meet the PP1 code (PMID: 16969763). This variant has been reported in at least 2 apparently unrelated probands (PMIDs: 34745198, 16969763). However, the number of individuals meeting one of the PS4 requirements of some functional vision impairment in affected males by age 30 years, and/or decreased or absent ERG responses was fewer than the requirement of at least 2 unrelated probands, so PS4_Supporting was not met. In summary, this variant is classified as likely 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 and PM2_Supporting. (date of approval 05/16/2025).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

PVS1

This is a nonsense 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).

PP1

The variant has been reported to segregate with retinal dystrophy through at least 1 affected meiosis from 1 family (PMID: 16969763).

PS4

This variant has been reported in at least 2 apparently unrelated probands (PMIDs: 34745198, 16969763). However, the number of individuals 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 was fewer than the requirement of at least 2 unrelated probands, so PS4_Supporting was not met.

Curation History

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