Submissions for variant NM_000180.4(GUCY2D):c.3098C>T (p.Ser1033Leu)

gnomAD frequency: 0.00106  dbSNP: rs146149224

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Leber Congenital Amaurosis/early Onset Retinal Dystrophy Variant Curation Expert Panel, ClinGen	RCV005053934	SCV005687741	likely benign	GUCY2D-related recessive retinopathy	2025-01-30	reviewed by expert panel	curation	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).
Eurofins Ntd Llc (ga)	RCV000585411	SCV000226559	uncertain significance	not provided	2018-06-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000585411	SCV000692893	uncertain significance	not provided	2017-08-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083338	SCV001100631	likely benign	Cone-rod dystrophy 6; Leber congenital amaurosis 1	2024-12-24	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003982924	SCV004799872	likely benign	GUCY2D-related disorder	2019-05-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).