Submissions for variant NM_000180.4(GUCY2D):c.1315G>A (p.Gly439Arg)

gnomAD frequency: 0.00006  dbSNP: rs140638938

Total submissions: 6

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	RCV005053943	SCV005687732	likely benign	GUCY2D-related recessive retinopathy	2025-01-30	reviewed by expert panel	curation	The NM_000180.4(GUCY2D):c.1315G>A (p.Gly439Arg) variant is predicted to replace the glycine at position p.439 with arginine. This variant is present in gnomAD v.4.1.0 at a GrpMax allele frequency of 0.001850 with 190 alleles / 90756 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 4 adult individuals in gnomAD which exceeds the LCA/eoRD VCEP threshold of ≥ 3 (gnomAD version 4.1.0; BS2_supporting). 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, BS2_supporting. (VCEP specifications version 1.0.0; date of approval 01/22/2025)
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000415352	SCV000492720	uncertain significance	Nystagmus; Abnormal electroretinogram	2014-07-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000487886	SCV000575086	uncertain significance	not provided	2016-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001078961	SCV001098551	likely benign	Cone-rod dystrophy 6; Leber congenital amaurosis 1	2024-07-31	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001198299	SCV001369183	uncertain significance	Choroidal dystrophy, central areolar, 1	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. This variant was inherited from a parent.
PreventionGenetics, part of Exact Sciences	RCV004748751	SCV005359837	uncertain significance	GUCY2D-related disorder	2024-09-06	no assertion criteria provided	clinical testing	The GUCY2D c.1315G>A variant is predicted to result in the amino acid substitution p.Gly439Arg. This variant was reported in an individual with Familial exudative vitreoretinopathy & high myopia (Supplemental Table 2, Wang et al. 2019. PubMed ID: 31106028). This variant is reported in 0.23% of alleles in individuals of South Asian descent in gnomAD. Although we suspect this variant may be benign, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.