Variant: NM_000180.4(GUCY2D):c.3098C>T (p.Ser1033Leu)

CA240817

194699 (ClinVar)

Gene: GUCY2D

Condition: GUCY2D-related recessive retinopathy

Inheritance Mode: Autosomal recessive inheritance

UUID: cff03494-6ff6-495d-8736-2fa8f4c27bae

Approved on: 2025-01-30

Published on: 2025-01-30

HGVS expressions

NM_000180.4:c.3098C>T
NM_000180.4(GUCY2D):c.3098C>T (p.Ser1033Leu)
NC_000017.11:g.8015981C>T
CM000679.2:g.8015981C>T
NC_000017.10:g.7919299C>T
CM000679.1:g.7919299C>T
NC_000017.9:g.7860024C>T
NG_009092.1:g.18312C>T
ENST00000254854.5:c.3098C>T
ENST00000254854.4:c.3098C>T
NM_000180.3:c.3098C>T

Likely Benign

• Met criteria codes: BS1 BP4

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

Evidence submitted by expert panel

Leber Congenital Amaurosis/early onset Retinal Dystrophy VCEP

The NM_000180.4(GUCY2D):c.3098C>T (p.Ser1033Leu) variant is predicted to replace the serine at position p.1033 with leucine. This variant is present in gnomAD v.4.1.0 at a GrpMax allele frequency of 0.003423, with 284 alleles / 75032 total alleles in the African/African American population, which is higher than the ClinGen LCA / eoRD VCEP BS1 threshold of >0.0016 (BS1). The computational predictor REVEL gives a score of 0.203, which is below the ClinGen LCA / eoRD VCEP threshold of ≤0.290 and predicts a non-damaging effect on RetGC-1 protein function. In addition, the splicing impact predictor SpliceAI gives a delta score of 0.00, which is below the ClinGen LCA/eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4). In summary, this variant meets the criteria to be classified as Likely Benign for GUCY2D-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP: BS1, BP4. (VCEP specifications version 1.0.0; date of approval 01/22/2025).

Met criteria codes

• BS1: This variant is present in gnomAD v.4.1.0 at a GrpMax allele frequency of 0.003423, with 284 alleles / 75032 total alleles in the African/African American population, which is higher than the ClinGen LCA / eoRD VCEP BS1 threshold of >0.0016 (BS1).
• BP4: The computational predictor REVEL gives a score of 0.203, which is below the ClinGen LCA / eoRD VCEP threshold of ≤0.290 and predicts a non-damaging effect on RetGC-1 function. In addition, the splicing impact predictor SpliceAI gives a delta score of 0.00, which is below the ClinGen LCA / eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4).