Submissions for variant NM_000180.4(GUCY2D):c.1672G>A (p.Asp558Asn)

gnomAD frequency: 0.00002  dbSNP: rs188568530

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Mendelics	RCV000989738	SCV001140282	uncertain significance	Cone-rod dystrophy 6	2019-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001070091	SCV001235301	uncertain significance	Cone-rod dystrophy 6; Leber congenital amaurosis 1	2024-01-13	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 558 of the GUCY2D protein (p.Asp558Asn). This variant is present in population databases (rs188568530, gnomAD 0.03%). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 31456290, 32865313). ClinVar contains an entry for this variant (Variation ID: 803314). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GUCY2D protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics	RCV002488082	SCV002779998	uncertain significance	Choroidal dystrophy, central areolar, 1; Cone-rod dystrophy 6; Leber congenital amaurosis 1; Night blindness, congenital stationary, type1i	2021-07-23	criteria provided, single submitter	clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001003038	SCV001161095	likely pathogenic	Leber congenital amaurosis	2019-06-23	no assertion criteria provided	research