ClinVar Miner

Submissions for variant NM_023067.4(FOXL2):c.855_871dup (p.His291fs)

dbSNP: rs797044532
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000192040 SCV000484898 pathogenic Blepharophimosis, ptosis, and epicanthus inversus syndrome 2016-11-03 criteria provided, single submitter clinical testing
GeneDx RCV000599160 SCV000710655 pathogenic not provided 2023-06-29 criteria provided, single submitter clinical testing Reported previously, using alternate nomenclature of 1092-1108dup17 or c.844_860dup17, in multiple individuals from at least two families affected with blepharophimosis, ptosis, epicanthus inversus syndrome (Crisponi et al., 2001; Yang et al., 2017).; Frameshift variant predicted to result in protein truncation in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28849110, 31048069, 31077882, 32454486, 20184535, 11776388, 12938087, 36338666, 11175783)
Wessex Regional Genetics Laboratory, Salisbury District Hospital RCV000192040 SCV000924443 pathogenic Blepharophimosis, ptosis, and epicanthus inversus syndrome 2018-01-01 criteria provided, single submitter clinical testing
Invitae RCV000599160 SCV003525289 pathogenic not provided 2023-10-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.His291Argfs*71) in the FOXL2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 86 amino acid(s) of the FOXL2 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This premature translational stop signal has been observed in individuals with blepharophimosis-ptosis-epicanthus inversus syndrome (PMID: 11175783, 28849110, 31048069). It has also been observed to segregate with disease in related individuals. This variant is also known as 1092_1108dup and c.844_860dup17. ClinVar contains an entry for this variant (Variation ID: 4866). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000005142 SCV000025319 pathogenic BLEPHAROPHIMOSIS, PTOSIS, AND EPICANTHUS INVERSUS, TYPE I 2003-09-01 no assertion criteria provided literature only
GeneReviews RCV000192040 SCV000207367 not provided Blepharophimosis, ptosis, and epicanthus inversus syndrome no assertion provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.