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_000180.4(GUCY2D):c.2766C>G (p.Tyr922Ter)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA287533367

587413 (ClinVar)

Gene: GUCY2D

Condition: GUCY2D-related recessive retinopathy

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: f812ad80-07cd-4204-b4bc-fee96a44f880

Approved on: 2025-01-31

Published on: 2025-01-31

HGVS expressions

NM_000180.4:c.2766C>G

NM_000180.4(GUCY2D):c.2766C>G (p.Tyr922Ter)

NC_000017.11:g.8015048C>G

CM000679.2:g.8015048C>G

NC_000017.10:g.7918366C>G

CM000679.1:g.7918366C>G

NC_000017.9:g.7859091C>G

NG_009092.1:g.17379C>G

ENST00000254854.5:c.2766C>G

ENST00000254854.4:c.2766C>G

NM_000180.3:c.2766C>G

Pathogenic

PVS1 PM3_Supporting PM2_Supporting

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 GUCY2D 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_000180.4(GUCY2D):c.2766C>G (p.Tyr922Ter) is a nonsense variant that introduces a premature stop codon into exon 15 of 20, 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 was homozygous for the variant (0.5 points, VCEP member-provided data, PM3_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for GUCY2D-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP: PVS1, PM2_Supporting, and PM3_Supporting. (VCEP specifications version 1.0.0; date of approval 01/22/2025).

PVS1

This is a nonsense variant that introduces a premature stop codon into exon 15 of 20, and is predicted to lead to nonsense-mediated decay in a gene in which loss-of-function is an established mechanism of disease (PVS1).

PM3_Supporting

This variant has been reported in at least 1 proband with early-onset severe retinal dystrophy who was homozygous for the variant (0.5 points, VCEP member-provided data, PM3_Supporting).

PM2_Supporting

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

Curation History

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