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 obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_000329.3(RPE65):c.1194C>T (p.Asp398=)

CA902256

298020 (ClinVar)

Gene: RPE65
Condition: RPE65-related recessive retinopathy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: d3beee9e-cde2-48f6-b974-09d878fa6c0b
Approved on: 2024-07-23
Published on: 2024-07-23

HGVS expressions

NM_000329.3:c.1194C>T
NM_000329.3(RPE65):c.1194C>T (p.Asp398=)
NC_000001.11:g.68431520G>A
CM000663.2:g.68431520G>A
NC_000001.10:g.68897203G>A
CM000663.1:g.68897203G>A
NC_000001.9:g.68669791G>A
NG_008472.1:g.23440C>T
NG_008472.2:g.23440C>T
ENST00000262340.6:c.1194C>T
ENST00000262340.5:c.1194C>T
NM_000329.2:c.1194C>T
More

Likely Benign

Met criteria codes 2
BP4 BP7
Not Met criteria codes 1
BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Leber Congenital Amaurosis/early onset Retinal Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RPE65 Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Leber Congenital Amaurosis/early onset Retinal Dystrophy VCEP
NM_000329.3(RPE65):c.978G>T (p.Val326=) is a silent variant located near the center of exon 11. This variant is present in gnomAD v.2.1.1 at a GrpMax allele frequency of 0.0003016, with 15 alleles / 30608 total alleles in the South Asian population, which is lower than the ClinGen LCA / eoRD VCEP BS1 threshold of >0.0008 and fails to meet this criterion. The splicing impact predictor SpliceAI gives a delta score of 0.01 for splice donor loss and splice donor gain, which is below the ClinGen LCA / eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4, BP7). In summary, this variant meets the criteria to be classified as likely benign for RPE65-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA / eoRD VCEP: BP4 and BP7. (VCEP specifications version 1.0.0; date of approval 09/21/2023).
Met criteria codes
BP4
There is no REVEL data for this variant. The splicing impact predictor SpliceAI gives a delta score of 0.01 for donor loss and donor gain, which is below the ClinGen LCA / eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4).
BP7
The splicing impact predictor SpliceAI gives a delta score of 0.01 for donor loss and donor gain, which is below the ClinGen LCA / eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP7).
Not Met criteria codes
BS1
This variant is present in gnomAD v.2.1.1 at a GrpMax allele frequency of 0.0003016, with 15/30608 in the South Asian population, which is lower than the ClinGen LCA / eoRD VCEP BS1 threshold of >0.0008 and fails to meet this criterion.
Curation History
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