Submissions for variant NM_000180.4(GUCY2D):c.154G>T (p.Ala52Ser)

gnomAD frequency: 0.29501  dbSNP: rs61749665

Total submissions: 16

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	RCV005053886	SCV005687735	benign	GUCY2D-related recessive retinopathy	2025-01-30	reviewed by expert panel	curation	The NM_000180.4(GUCY2D):c.154G>T (p.Ala52Ser) variant is predicted to replace the alanine at position p.52 with serine. This variant is present in gnomAD v.4.1.0 at a GrpMax allele frequency of 0.6857, with 26306 alleles / 37974 total alleles in the East Asian population, which is higher than the ClinGen LCA / eoRD VCEP BA1 threshold of >0.016 (BA1). This variant has been found in the homozygous state in 95,479 adult individuals in gnomAD v4.1.0 (BS2). The computational predictor REVEL gives a score of 0.126, which is below the ClinGen LCA / eoRD VCEP threshold of ≤0.183 and predicts a non-damaging effect on RetGC-1 protein function. In addition, the splicing impact predictor SpliceAI gives a delta score of 0.0, which is below the ClinGen LCA / eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4_Moderate). 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: BA1, BS2, BP4_Moderate. (VCEP specifications version 1.0.0; date of approval 01/22/2025).
Eurofins Ntd Llc (ga)	RCV000078318	SCV000110164	benign	not specified	2016-03-16	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078318	SCV000302884	benign	not specified		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001518075	SCV001726709	benign	Cone-rod dystrophy 6; Leber congenital amaurosis 1	2025-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000084835	SCV001751694	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000084835	SCV002049064	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Molecular Genetics, Royal Melbourne Hospital	RCV002225071	SCV002503738	benign	Cone-rod dystrophy 6	2021-10-04	criteria provided, single submitter	clinical testing	Population allele frequency is 40% (rs61749665, 54,832/138,790 alleles in gnomAD v2.0.2). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria met: BA1
Fulgent Genetics, Fulgent Genetics	RCV002490349	SCV002802295	benign	Choroidal dystrophy, central areolar, 1; Cone-rod dystrophy 6; Leber congenital amaurosis 1; Night blindness, congenital stationary, type1i	2021-09-01	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000084835	SCV005251556	benign	not provided		criteria provided, single submitter	not provided
OMIM	RCV000009947	SCV000030168	pathogenic	Leber congenital amaurosis 1	1998-08-01	flagged submission	literature only
Retina International	RCV000084835	SCV000116971	not provided	not provided		no assertion provided	not provided
Department of Ophthalmology and Visual Sciences Kyoto University	RCV000084835	SCV000172504	probable-non-pathogenic	not provided		no assertion criteria provided	not provided	Converted during submission to Likely benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000078318	SCV001740881	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000078318	SCV001921526	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000078318	SCV001956221	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000078318	SCV001972869	benign	not specified		no assertion criteria provided	clinical testing