Submissions for variant NM_024513.4(FYCO1):c.3456G>A (p.Trp1152Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV003226076	SCV003922194	likely pathogenic	Cataract 18	2023-05-02	criteria provided, single submitter	curation	The homozygous p.Trp1152Ter variant in FYCO1 was identified by our study in one individual with developmental cataracts. The p.Trp1152Ter variant in FYCO1 has not been previously reported in individuals with cataract 18 but has been identified in 0.003% (1/30614) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs774761672). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 1152, which is predicted to lead to a truncated or absent protein. Loss of function of the FYCO1 gene is an established disease mechanism in autosomal recessive cataract 18. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive cataract 18. ACMG/AMP Criteria applied: PVS1, PM2_Supporting (Richards 2015).
CeGaT Center for Human Genetics Tuebingen	RCV003435999	SCV004154342	likely pathogenic	not provided	2023-01-01	criteria provided, single submitter	clinical testing	FYCO1: PVS1