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.28+2T>C

CA412746845

Gene: RPGR (HGNC:6103)

Condition: RPGR-related retinopathy (MONDO:0100437)

Inheritance Mode: X-linked inheritance

UUID: d7141b55-3ee4-4e0a-a1c9-6d464eb14293

Approved on: 2026-09-26

Published on: 2026-09-26

HGVS expressions

NM_001034853.2:c.28+2T>C

NC_000023.11:g.38327338A>G

CM000685.2:g.38327338A>G

NC_000023.10:g.38186591A>G

CM000685.1:g.38186591A>G

NC_000023.9:g.38071535A>G

NG_009553.1:g.5198T>C

ENST00000642373.1:c.28+2T>C

ENST00000642395.2:c.28+2T>C

ENST00000642558.1:c.28+2T>C

ENST00000642739.1:c.28+2T>C

ENST00000644238.1:c.28+2T>C

ENST00000644337.1:c.28+2T>C

ENST00000645032.1:c.28+2T>C

ENST00000645124.1:c.28+2T>C

ENST00000646020.1:c.28+2T>C

ENST00000647261.1:c.28+2T>C

ENST00000318842.11:c.28+2T>C

ENST00000339363.7:c.28+2T>C

ENST00000378505.6:c.28+2T>C

ENST00000465127.1:c.172-338783A>G

ENST00000474584.5:c.28+2T>C

ENST00000482855.5:c.28+2T>C

NM_000328.2:c.28+2T>C

NM_001034853.1:c.28+2T>C

NM_001367245.1:c.28+2T>C

NM_001367246.1:c.28+2T>C

NM_001367247.1:c.28+2T>C

NM_001367249.1:c.28+2T>C

NM_001367250.1:c.28+2T>C

NM_001367251.1:c.28+2T>C

NR_159803.1:n.170+2T>C

NR_159804.1:n.170+2T>C

NR_159805.1:n.170+2T>C

NR_159806.1:n.170+2T>C

NR_159807.1:n.170+2T>C

NM_000328.3:c.28+2T>C

Pathogenic

PVS1 PS1_Supporting PM2_Supporting

PS4 PP4

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

X-linked Inherited Retinal Disease VCEP

The NM_001034853.2(RPGR):c.28+2T>C variant is a canonical splice site variant in intron 1, located 2 nucleotides before exon 1. This variant occurs at a canonical splice site in intron 1 and is predicted to disrupt splicing and induce skipping of exon 1, which is expected to introduce a premature stop codon in RPGR (PVS1). This variant is found in the +/- 1,2 dinucleotide and meets PVS1 (met) and another variant, c.28+1G>A, was previously classified as pathogenic in the same donor/acceptor +/-1,2 dinucleotide for the RPGR-related retinopathy by ClinGen X-linked IRD VCEP (PS1_supporting). This variant is absent from hemizygous individuals in gnomAD v4.1.0 (PM2_Supporting). This variant has been reported in at least 2 apparently unrelated probands (PMID: 30105367, 36819107). However, the number of individuals meeting the PS4 requirement of being 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 was fewer than the requirement of at least 2 unrelated probands, so PS4_Supporting was not met. 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, PS1_Supporting, and PM2_Supporting.

PVS1

This variant occurs at a canonical splice site in intron 1 and is predicted to disrupt splicing and induce skipping of exon 1, which is expected to introduce a premature stop codon in RPGR (PVS1).

PS1_Supporting

This variant is found in the +/- 1,2 dinucleotide and meets PVS1 (met) and another variant, c.28+1G>A, was previously classified as pathogenic in the same donor/acceptor +/-1,2 dinucleotide for the RPGR-related retinopathy by ClinGen X-linked IRD VCEP (PS1_supporting).

PM2_Supporting

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

PS4

This variant has been reported in at least 2 apparently unrelated probands (PMID: 30105367, 36819107). However, the number of individuals meeting the PS4 requirement of being 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 was fewer than the requirement of at least 2 unrelated probands, so PS4_Supporting was not met.

PP4

This variant has been reported in at least 2 apparently unrelated probands (PMID: 30105367, 36819107), no detailed individual level data meeting PP4 requirements was provided.

Curation History

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