Submissions for variant NM_000503.6(EYA1):c.775C>T (p.Gln259Ter)

dbSNP: rs2128999627

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001980140	SCV002229614	pathogenic	Melnick-Fraser syndrome	2020-11-25	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with EYA1-related conditions. For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln259*) in the EYA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EYA1 are known to be pathogenic (PMID: 10464653, 18220287).
Molecular Genetics Department, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology	RCV003985859	SCV004801784	likely pathogenic	Branchiootorenal syndrome 1		criteria provided, single submitter	clinical testing	A previously undescribed nucleotide variant creates a premature translation stop signal p.Gln259Ter in the EYA1 gene. The variant was observed in heterozygous state in an individual affected with branchiotorenal syndrome. Loss-of-function variants are reported in patients with Branchiootorenal syndrome 1, with or without cataracts, 113650. The variant is not present in population database (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as likely pathogenic.