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.2101G>T

CA412731451

Gene: RPGR (HGNC:6103)

Condition: RPGR-related retinopathy (MONDO:0100437)

Inheritance Mode: X-linked inheritance (primarily recessive with milder female expression)

UUID: 56f6daef-8cbf-497b-bded-49d18392a82b

Approved on: 2025-09-07

Published on: 2025-09-07

HGVS expressions

NM_001034853.2:c.2101G>T

NC_000023.11:g.38286898C>A

CM000685.2:g.38286898C>A

NC_000023.10:g.38146151C>A

CM000685.1:g.38146151C>A

NC_000023.9:g.38031095C>A

NG_009553.1:g.45638G>T

ENST00000494707.6:c.953+967G>T

ENST00000642170.1:n.1826+4061G>T

ENST00000642395.2:c.1905+196G>T

ENST00000642739.1:c.1572+4061G>T

ENST00000644238.1:c.1386+4061G>T

ENST00000644337.1:c.1719+196G>T

ENST00000645032.1:c.2101G>T

ENST00000645124.1:c.*101+196G>T

ENST00000646020.1:c.*594+196G>T

ENST00000318842.11:c.1905+196G>T

ENST00000339363.7:c.2520+196G>T

ENST00000378505.6:c.2101G>T

ENST00000465127.1:c.172-379223C>A

ENST00000474584.5:c.*37+4061G>T

ENST00000482855.5:c.1905+196G>T

ENST00000494707.5:c.139+4061G>T

NM_000328.2:c.1905+196G>T

NM_001034853.1:c.2101G>T

NM_001367245.1:c.1902+196G>T

NM_001367246.1:c.1719+196G>T

NM_001367247.1:c.1572+4061G>T

NM_001367248.1:c.1602+4061G>T

NM_001367249.1:c.1569+4061G>T

NM_001367250.1:c.1569+4061G>T

NM_001367251.1:c.1386+4061G>T

NR_159803.1:n.2263+196G>T

NR_159804.1:n.1648+4061G>T

NR_159805.1:n.1714+4061G>T

NR_159806.1:n.1866+196G>T

NR_159807.1:n.1622+4061G>T

NR_159808.1:n.1826+4061G>T

NM_000328.3:c.1905+196G>T

Likely Pathogenic

PVS1 PM2_Supporting

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.2101G>T (p.Glu701Ter) is a nonsense variant introducing a premature stop in codon 701 within exon 15 of 15 that is predicted to disrupt a critical C-terminal region required for proper glutamylation of RPGR (PVS1, PMID: 36445968). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). This variant has been reported in a submission to the Leiden Open Variation Database (LOVD 3.0) as a disease-causing variant (DB-ID RPGR_000065), however, no affected individual was described meeting one of the PS4 requirements of some functional vision impairment in an affected male by age 30 years, or decreased or absent electroretinogram responses, 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.

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).

PM2_Supporting

This variant is absent from gnomAD v4.0.0 (PM2_Supporting).

PS4

This variant has been reported in a submission to the Leiden Open Variation Database (LOVD 3.0) as a disease-causing variant (DB-ID RPGR_000065), however, no affected individual was described meeting one of the PS4 requirements of some functional vision impairment in an affected male by age 30 years, or decreased or absent cone and/or rod electroretinogram responses, so PS4_Supporting was not met.

Curation History

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