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.2176G>T

CA412731265

Gene: RPGR (HGNC:6103)

Condition: RPGR-related retinopathy (MONDO:0100437)

Inheritance Mode: X-linked inheritance

UUID: 78072885-ea95-440e-981a-a7296e774d0e

Approved on: 2025-08-03

Published on: 2025-08-04

HGVS expressions

NM_001034853.2:c.2176G>T

NC_000023.11:g.38286823C>A

CM000685.2:g.38286823C>A

NC_000023.10:g.38146076C>A

CM000685.1:g.38146076C>A

NC_000023.9:g.38031020C>A

NG_009553.1:g.45713G>T

ENST00000494707.6:c.953+1042G>T

ENST00000642170.1:n.1826+4136G>T

ENST00000642395.2:c.1905+271G>T

ENST00000642739.1:c.1572+4136G>T

ENST00000644238.1:c.1386+4136G>T

ENST00000644337.1:c.1719+271G>T

ENST00000645032.1:c.2176G>T

ENST00000645124.1:c.*101+271G>T

ENST00000646020.1:c.*594+271G>T

ENST00000318842.11:c.1905+271G>T

ENST00000339363.7:c.2520+271G>T

ENST00000378505.6:c.2176G>T

ENST00000465127.1:c.172-379298C>A

ENST00000474584.5:c.*37+4136G>T

ENST00000482855.5:c.1905+271G>T

ENST00000494707.5:c.139+4136G>T

NM_000328.2:c.1905+271G>T

NM_001034853.1:c.2176G>T

NM_001367245.1:c.1902+271G>T

NM_001367246.1:c.1719+271G>T

NM_001367247.1:c.1572+4136G>T

NM_001367248.1:c.1602+4136G>T

NM_001367249.1:c.1569+4136G>T

NM_001367250.1:c.1569+4136G>T

NM_001367251.1:c.1386+4136G>T

NR_159803.1:n.2263+271G>T

NR_159804.1:n.1648+4136G>T

NR_159805.1:n.1714+4136G>T

NR_159806.1:n.1866+271G>T

NR_159807.1:n.1622+4136G>T

NR_159808.1:n.1826+4136G>T

NM_000328.3:c.1905+271G>T

Pathogenic

PS4_Supporting PM2_Supporting PVS1

BP7 BP3 BS1 PM5 PM4 BA1 PS1

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.2176G>T (p.Glu726Ter) is a nonsense variant that substitutes a premature stop codon for amino acid 726 within exon 15 of 15, which disrupts 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 at least 2 apparently unrelated probands meeting one of the PS4 requirements of a male with some functional vision impairment by age 30 years and/or decreased or absent electroretinogram responses, or a female with functional visual abnormality and documentation of a male relative affected with retinitis pigmentosa (PMID: 21857984, PMID: 17325176, PS4_Supporting). 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_Supporting, and PM2_Supporting. (date of approval 05/16/2025).

PS4_Supporting

This variant has been reported in at least 2 apparently unrelated probands meeting one of the PS4 requirements of a male with some functional vision impairment by age 30 and/or decreased or absent ERG responses, or a female with functional visual abnormality and documentation of a male relative affected with retinitis pigmentosa (PMID: 21857984, PMID: 17325176, PS4_Supporting).

PM2_Supporting

This variant is absent from gnomAD v4.1.0 (PM2_Supporting).

PVS1

This is a nonsense variant 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).

BP7

Causes amino acid change so not silent

BP3

No indels

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM5

Not previously curated

PM4

No indels

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS1

Not previously curated

Curation History

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