Submissions for variant NM_005249.5(FOXG1):c.275C>T (p.Ala92Val)

gnomAD frequency: 0.00001  dbSNP: rs1057520147

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV003448303	SCV004175929	likely benign	FOXG1 disorder	2023-10-13	reviewed by expert panel	curation	The p.Ala92Val variant in FOXG1 is observed in at least 1 unaffected individual (internal database - Invitae) (BS2_supporting). The p.Ala92Val variant is found in at least 2 patients with an alternate molecular basis of disease (internal database - Invitae) (BP5). Computational analysis prediction tools suggest that the p.Ala92Val variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). The p.Ala92Val variant in FOXG1 is absent from gnomAD (PM2_supporting). In the absence of other pathogenic evidence beyond PM2_Supporting, and because this variant has been observed in 1 unaffected individual and 2 individuals with an alternate molecular diagnosis, the ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel has agreed to overrule the PM2_Supporting criterion and classified this variant as Likely Benign (BS2_supporting, BP4, BP5).
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000429748	SCV000511406	uncertain significance	not provided	2016-09-28	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Invitae	RCV000685886	SCV000813386	benign	Rett syndrome, congenital variant	2022-10-03	criteria provided, single submitter	clinical testing