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.1697G>A (p.Gly566Glu)

CA146040

92855 (ClinVar)

Gene: RPGR
Condition: RPGR-related retinopathy
Inheritance Mode: X-linked inheritance (dominant (HP:0001423))
Link to MONDO
UUID: 95c115ba-ae82-41b3-a96e-2e80e4e189d9
Approved on: 2025-05-20
Published on: 2025-05-20

HGVS expressions

NM_001034853.2:c.1697G>A
NM_001034853.2(RPGR):c.1697G>A (p.Gly566Glu)
NC_000023.11:g.38287917C>T
CM000685.2:g.38287917C>T
NC_000023.10:g.38147170C>T
CM000685.1:g.38147170C>T
NC_000023.9:g.38032114C>T
NG_009553.1:g.44619G>A
ENST00000494707.6:c.901G>A
ENST00000642170.1:n.1826+3042G>A
ENST00000642395.2:c.1697G>A
ENST00000642739.1:c.1572+3042G>A
ENST00000644238.1:c.1386+3042G>A
ENST00000644337.1:c.1511G>A
ENST00000645032.1:c.1697G>A
ENST00000645124.1:c.1573-672G>A
ENST00000646020.1:c.*390G>A
ENST00000318842.11:c.1697G>A
ENST00000339363.7:c.1697G>A
ENST00000378505.6:c.1697G>A
ENST00000465127.1:c.172-378204C>T
ENST00000474584.5:c.*37+3042G>A
ENST00000482855.5:c.1697G>A
ENST00000494707.5:c.139+3042G>A
NM_000328.2:c.1697G>A
NM_001034853.1:c.1697G>A
NM_001367245.1:c.1694G>A
NM_001367246.1:c.1511G>A
NM_001367247.1:c.1572+3042G>A
NM_001367248.1:c.1602+3042G>A
NM_001367249.1:c.1569+3042G>A
NM_001367250.1:c.1569+3042G>A
NM_001367251.1:c.1386+3042G>A
NR_159803.1:n.2059G>A
NR_159804.1:n.1648+3042G>A
NR_159805.1:n.1714+3042G>A
NR_159806.1:n.1715-672G>A
NR_159807.1:n.1622+3042G>A
NR_159808.1:n.1826+3042G>A
NM_000328.3:c.1697G>A
More

Benign

Met criteria codes 2
BA1 BP4
Not Met criteria codes 1
BS3

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
The NM_001034853.2(RPGR):c.1697G>A (p.Gly566Glu) variant is a missense variant encoding the substitution of Glycine with Glutamic acid at amino acid 566. This variant is present in gnomAD v.4.1.0 at a frequency of 0.06732 among hemizygous individuals, with 26691 variant alleles / 396470 total alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.00005 (BA1). This variant was shown to have normal protein function and localization (PMID: 30622176). The computational predictor REVEL gives a score of 0.063, 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 0.05, 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 likely 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 and BP4_moderate (date of approval 05/15/2025).
Met criteria codes
BA1
This variant is present in gnomAD v.4.1.0 at a frequency of 0.06732 among hemizygous individuals, with 26691 variant alleles / 396470 total alleles, which is higher than the ClinGen X-linked IRD VCEP BA1 threshold of >0.00005 (BA1).
BP4
The computational predictor REVEL gives a score of 0.063, 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 0.05, 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).
Not Met criteria codes
BS3
This variant was shown to have normal protein interactions and localization. Code N/A.
Curation History
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