Submissions for variant NM_012186.3(FOXE3):c.289A>G (p.Ile97Val)

dbSNP: rs774505755

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
3billion	RCV001267882	SCV002521642	likely pathogenic	Congenital primary aphakia	2022-05-22	criteria provided, single submitter	clinical testing	The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.78; 3Cnet: 0.78). Same nucleotide change resulting in same amino acid change (ClinVar ID: VCV000983475) and a different missense change at the same codon (p.Ile97Met, ClinVar ID: VCV000935371 / PMID: 29878917) have been reported to be associated with FOXE3 related disorder.The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 20806047, 25148791, 26995144, 34046667) and co-segregate with the disease in at least 3 similarly affected relatives/individuals in the same family or similarly affected unrelated family (PMID: 32976546). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Laboratory of NeuroGenetics and Regenerative Medicine, University of Maryland School of Medicine	RCV001267882	SCV001296388	likely pathogenic	Congenital primary aphakia		no assertion criteria provided	research
Human Developmental Genetics Laboratory, Medical College of Wisconsin	RCV001267882	SCV001593182	pathogenic	Congenital primary aphakia	2021-05-01	no assertion criteria provided	research