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
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Variant: NM_000180.4(GUCY2D):c.129_134del (p.Leu44_Leu45del)

CA8365473

283615 (ClinVar)

Gene: GUCY2D
Condition: GUCY2D-related recessive retinopathy
Inheritance Mode: Autosomal recessive inheritance
UUID: 823c36b3-bd9e-4671-994a-adefcdb0d77d
Approved on: 2025-01-30
Published on: 2025-01-30

HGVS expressions

NM_000180.4:c.129_134del
NM_000180.4(GUCY2D):c.129_134del (p.Leu44_Leu45del)
NC_000017.11:g.8003176_8003181del
CM000679.2:g.8003176_8003181del
NC_000017.10:g.7906494_7906499del
CM000679.1:g.7906494_7906499del
NC_000017.9:g.7847219_7847224del
NG_009092.1:g.5507_5512del
ENST00000254854.5:c.129_134del
ENST00000254854.4:c.129_134del
NM_000180.3:c.129_134del
More

Benign

Met criteria codes 2
BS2 BS1
Not Met criteria codes 1
PM3

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 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
The NM_000180.4(GUCY2D):c.129_134del (p.Leu44_Leu45del) variant is the deletion of 2 amino acids from a repetitive region of the protein's leader sequence. This variant is present in gnomAD v4.1.0 at a GrpMax allele frequency of 0.005906, with 514 alleles / 80814 total alleles in the South Asian population, which is higher than the ClinGen LCA/eoRD VCEP BS1 threshold of >0.0016 (BS1). This variant has been found in the homozygous state in 21 adult individuals in gnomAD which exceeds the LCA/eoRD VCEP threshold of ≥6 (gnomAD version 4.1.0; BS2). In summary, this variant meets the criteria to be classified as Benign for GUCY2D-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP: BS1, BS2. (VCEP specifications version 1.0.0; date of approval 01/22/2025).
Met criteria codes
BS2
This variant has been found in the homozygous state in 21 adult individuals in gnomAD which exceeds the LCA/eoRD VCEP threshold of ≥6 (gnomAD version 4.1.0; BS2)
BS1
This variant is present in gnomAD v.4.1.0 at a GrpMax allele frequency of 0.005906, with 514 alleles / 80814 total alleles in the South Asian population, which is higher than the ClinGen LCA / eoRD VCEP BS1 threshold of >0.0016 (BS1).
Not Met criteria codes
PM3
Although there are at least 2 patients with a diagnosis of LCA reported with p.Leu44_Leu45del, one homozygous and one heterozygous with a pathogenic variant (phase unknown), the variant is not sufficiently rare to be considered for this code.
Curation History
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