Submissions for variant NM_145649.5(GCNT2):c.1046A>G (p.Tyr349Cys)

gnomAD frequency: 0.00009  dbSNP: rs148284531

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001047410	SCV001211367	pathogenic	Cataract 13 with adult I phenotype	2019-12-31	criteria provided, single submitter	clinical testing	This variant has been observed in individual(s) with congenital cataracts (PMID: 22935719, 25457163, Invitae). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is present in population databases (rs148284531, ExAC 0.009%). This sequence change replaces tyrosine with cysteine at codon 347 of the GCNT2 protein (p.Tyr347Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV001047410	SCV004805130	likely pathogenic	Cataract 13 with adult I phenotype	2024-03-17	criteria provided, single submitter	research