Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: RPGR vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001034853.2(RPGR):c.2341G>A (p.Ala781Thr)

CA10385291

257193 (ClinVar)

Gene: RPGR
Condition: RPGR-related retinopathy
Inheritance Mode: X-linked inheritance (dominant (HP:0001423))
Link to MONDO
UUID: d58d7e83-839e-4769-99dd-f1ceec6d5e38
Approved on: 2025-05-20
Published on: 2025-05-21

HGVS expressions

NM_001034853.2:c.2341G>A
NM_001034853.2(RPGR):c.2341G>A (p.Ala781Thr)
NC_000023.11:g.38286658C>T
CM000685.2:g.38286658C>T
NC_000023.10:g.38145911C>T
CM000685.1:g.38145911C>T
NC_000023.9:g.38030855C>T
NG_009553.1:g.45878G>A
ENST00000494707.6:c.953+1207G>A
ENST00000642170.1:n.1826+4301G>A
ENST00000642395.2:c.1905+436G>A
ENST00000642739.1:c.1572+4301G>A
ENST00000644238.1:c.1386+4301G>A
ENST00000644337.1:c.1719+436G>A
ENST00000645032.1:c.2341G>A
ENST00000645124.1:c.*101+436G>A
ENST00000646020.1:c.*594+436G>A
ENST00000318842.11:c.1905+436G>A
ENST00000339363.7:c.2520+436G>A
ENST00000378505.6:c.2341G>A
ENST00000465127.1:c.172-379463C>T
ENST00000474584.5:c.*37+4301G>A
ENST00000482855.5:c.1905+436G>A
ENST00000494707.5:c.139+4301G>A
NM_000328.2:c.1905+436G>A
NM_001034853.1:c.2341G>A
NM_001367245.1:c.1902+436G>A
NM_001367246.1:c.1719+436G>A
NM_001367247.1:c.1572+4301G>A
NM_001367248.1:c.1602+4301G>A
NM_001367249.1:c.1569+4301G>A
NM_001367250.1:c.1569+4301G>A
NM_001367251.1:c.1386+4301G>A
NR_159803.1:n.2263+436G>A
NR_159804.1:n.1648+4301G>A
NR_159805.1:n.1714+4301G>A
NR_159806.1:n.1866+436G>A
NR_159807.1:n.1622+4301G>A
NR_159808.1:n.1826+4301G>A
NM_000328.3:c.1905+436G>A
More

Benign

Met criteria codes 3
BA1 BS2 BP4

Evidence Links 0

Expert Panel

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.2341G>A (p.Ala781Thr) is a missense variant encoding the substitution of alanine with threonine at amino acid 781. This variant is present in gnomAD v.4.1.0 at a frequency of 0.1538 among hemizygous individuals, with 54,741 variant alleles / 356,024 total alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.00005 (BA1). This variant has been identified in 13 healthy individuals meeting the BS2 requirement of no electroretinogram defects by the age of 30 years (PMIDs: 12657579, 18552978, 18552978, 32679846, BS2). The computational predictor REVEL gives a score of 0.059, which is below the ClinGen X-linked IRD VCEP threshold of <0.183 and predicts a non-damaging effect on RPGR function. Additionally, the splicing impact predictor SpliceAI gives a delta score of 0.00, which is below the ClinGen X-linked IRD VCEP recommended threshold of <0.1 and does not strongly predict an impact on splicing (BP4_moderate). In summary, this variant is classified as benign 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; BA1, BS2, and BP4_moderate. (date of approval 05/16/2025).
Met criteria codes
BA1
This variant is present in gnomAD v.4.1.0 at a frequency of 0.1538 among hemizygous individuals, with 54741 variant alleles / 356024 total alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.00005 (BA1).
BS2
This Variant has been identified in 13 healthy individuals meeting the BS2 requirements (>30 with ERG), PMID 12657579. Other PMIDs (18552978, 18552978, 32679846) found this variant but did not elaborate on the finding. The classification of benign was pulled out of the gnomAD database (BS2_strong).
BP4
The computational predictor REVEL gives a score of 0.059, which is below the ClinGen X-linked IRD VCEP threshold of < 0.183 and predicts a non-damaging effect on RPGR function. Additionally, the splicing impact predictor SpliceAI gives a delta score of 0.00, which is below the ClinGen X-linked IRD VCEP recommended threshold of <0.1 and does not strongly predict an impact on splicing (BP4_moderate).
Curation History
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