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_025114.4(CEP290):c.3462dup (p.Leu1155fs)

CA1139662802

813157 (ClinVar)

Gene: CEP290

Condition: CEP290-related ciliopathy (MONDO:0100451)

Inheritance Mode: Autosomal recessive inheritance

UUID: d3659ac7-07bf-44f0-8773-53825ed30815

Approved on: 2026-07-20

Published on: 2026-07-20

HGVS expressions

NM_025114.4:c.3462dup

NM_025114.4(CEP290):c.3462dup (p.Leu1155fs)

NC_000012.12:g.88092683dup

CM000674.2:g.88092683dup

NC_000012.11:g.88486460dup

CM000674.1:g.88486460dup

NC_000012.10:g.87010591dup

NG_008417.1:g.54536dup

NG_008417.2:g.54536dup

ENST00000309041.12:c.3461dup

ENST00000547691.8:c.745dup

ENST00000552810.6:c.3461dup

ENST00000672414.2:c.*1632dup

ENST00000672647.1:n.1821dup

ENST00000673058.2:c.3461dup

ENST00000674971.1:c.3461dup

ENST00000675089.1:c.287-1842dup

ENST00000675230.1:c.3440dup

ENST00000675408.1:c.3461dup

ENST00000675476.1:c.4322dup

ENST00000675628.1:n.3688dup

ENST00000675794.1:c.*1632dup

ENST00000675833.1:c.4229dup

ENST00000676074.1:c.3461dup

ENST00000676181.1:n.1149dup

ENST00000676363.1:n.9187dup

ENST00000676448.1:c.*1374dup

ENST00000309041.11:c.3467dup

ENST00000547691.6:c.641dup

ENST00000552810.5:c.3461dup

NM_025114.3:c.3461dup

NM_025114.4:c.3461dup

Likely Pathogenic

PVS1 PM2_Supporting

PM3

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 CEP290 Version 1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Leber Congenital Amaurosis/early onset Retinal Dystrophy VCEP

NM_025114.4(CEP290):c.3461dup (p.Leu1155ThrfsTer6) is a frameshift variant that introduces a premature stop codon into exon 30 of 54 and is predicted to lead to nonsense-mediated decay in a gene in which loss-of-function is an established mechanism of disease (PVS1). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). This variant has been reported in at least 1 proband with early-onset severe retinal dystrophy who harbored the variant in the compound heterozygous state with the NM_025114.4(CEP290):c.2T>A (p.Met1Lys) variant suspected in trans (PMID: 32531858). However, the proband was not counted for PM3 in order to avoid circularity. There is an additional report of the variant in an inherited retinal disease cohort (PMID: 36460718) but no additional details were available. In summary, this variant meets the criteria to be classified as Likely Pathogenic for CEP290-related ciliopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP: PVS1 and PM2_Supporting. (LCA/eoRD VCEP Specifications for CEP290 Version 1.0.0)

PVS1

This is a frameshift variant that introduces a premature stop codon into exon 30 of 54 and is predicted to lead to nonsense-mediated decay in a gene in which loss-of-function is an established mechanism of disease (PVS1).

PM2_Supporting

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

PM3

This variant has been reported in at least 1 proband with early-onset severe retinal dystrophy who harbored the variant in the compound heterozygous state with the NM_025114.4(CEP290): p.Met1Lys variant suspected in trans (PMID: 32531858). However, the proband was not counted for PM3 in order to avoid circularity. There is an additional report of the variant in an IRD cohort (PMID: 36460718) but no additional details were available.

Curation History

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