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]

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Variant: NM_000329.3(RPE65):c.1244-5C>T

CA902225

772770 (ClinVar)

Gene: RPE65

Condition: RPE65-related recessive retinopathy

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: aff9e7a3-efae-4cab-ad76-1046ce21a3c1

Approved on: 2024-02-20

Published on: 2024-02-20

HGVS expressions

NM_000329.3:c.1244-5C>T

NM_000329.3(RPE65):c.1244-5C>T

NC_000001.11:g.68431381G>A

CM000663.2:g.68431381G>A

NC_000001.10:g.68897064G>A

CM000663.1:g.68897064G>A

NC_000001.9:g.68669652G>A

NG_008472.1:g.23579C>T

NG_008472.2:g.23579C>T

ENST00000262340.6:c.1244-5C>T

ENST00000262340.5:c.1244-5C>T

NM_000329.2:c.1244-5C>T

Likely Benign

PP3 BS1

Evidence Links 0

Expert Panel

Leber Congenital Amaurosis/early onset Retinal Dystrophy VCEP

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.1244-5C>T is a non-coding variant in intron 11 near the junction with exon 12. This variant is present in gnomAD v.2.1.1 at a GrpMax allele frequency of 0.002561, with 70 alleles / 24966 total alleles in the African/African-American population, which is higher than the ClinGen LCA / eoRD VCEP BS1 threshold of >0.0008 (BS1). The splicing impact predictor SpliceAI gives scores of 0.26 for acceptor gain and 0.20 for donor gain, which are above the ClinGen LCA / eoRD VCEP recommended threshold of ≥0.2 and predict a damaging impact on splicing (PP3). 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: BS1 and PP3 (VCEP specifications version 1.0.0; date of approval 09/21/2023).

PP3

The splicing impact predictor SpliceAI gives scores of 0.26 for acceptor gain and 0.20 for donor gain, which are above the ClinGen LCA / eoRD VCEP recommended threshold of ≥0.2 and predict a damaging impact on splicing (PP3).

BS1

This variant is present in gnomAD v.2.1.1 at a GrpMax allele frequency of 0.002561, with 70 alleles / 24966 total alleles in the African/African-American population, which is higher than the ClinGen LCA / eoRD VCEP BS1 threshold of >0.0008 (BS1).

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