Submissions for variant NM_020989.4(CRYGC):c.475dup (p.Ala159fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003759200	SCV004455416	uncertain significance	Nuclear pulverulent cataract	2023-04-15	criteria provided, single submitter	clinical testing	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with CRYGC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala159Glyfs*5) in the CRYGC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the CRYGC protein.
PreventionGenetics, part of Exact Sciences	RCV003901272	SCV004712627	pathogenic	CRYGC-related disorder	2023-10-30	criteria provided, single submitter	clinical testing	The CRYGC c.475dupG variant is predicted to result in a frameshift and premature protein termination (p.Ala159Glyfs*5). This variant occurs within the terminal exon of the CRYGC gene, near the stop codon. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At PreventionGenetics, we have detected this variant in another patient with childhood-onset cataracts (Internal Data). Frameshift variants in CRYGC are expected to be pathogenic and have been documented both up- and downstream of amino acid 159 in individuals with cataracts (Human Gene Mutation Database). This variant is interpreted as pathogenic.