ClinVar Miner

Submissions for variant NM_000325.6(PITX2):c.412-11A>G

dbSNP: rs1198152064
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001574968 SCV001801874 pathogenic not provided 2024-03-22 criteria provided, single submitter clinical testing Published functional studies demonstrate a splicing shift to a new acceptor site leading to an abnormal protein product containing 138 correct PITX2 residues followed by 117 incorrect amino acids (PMID: 16834779); Not observed in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Referred to as c.253-11A>G using alternate nomenclature; This variant is associated with the following publications: (PMID: 29939776, 34745210, 20881294, 8944018, 30457409, 31359131, 21730847, 11821690, 28730073, 19764918, 22569110, 16834779)
Human Developmental Genetics Laboratory, Medical College of Wisconsin RCV000008554 SCV002538929 pathogenic Axenfeld-Rieger syndrome type 1 2022-06-23 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV002512913 SCV003525862 pathogenic Axenfeld-Rieger syndrome type 1; Anterior segment dysgenesis 4 2022-05-27 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Studies have shown that this variant alters PITX2 gene expression (PMID: 28730073). ClinVar contains an entry for this variant (Variation ID: 8086). This variant is also known as IVS5- 11A>G. This variant has been observed in individuals with Axenfeld-Rieger syndrome (PMID: 8944018, 20881294, 28730073). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 4 of the PITX2 gene. It does not directly change the encoded amino acid sequence of the PITX2 protein.
OMIM RCV000008554 SCV000028762 pathogenic Axenfeld-Rieger syndrome type 1 1996-12-01 no assertion criteria 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.