Submissions for variant NM_025074.7(FRAS1):c.7551T>A (p.Tyr2517Ter)

gnomAD frequency: 0.00001  dbSNP: rs745597204

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000223984	SCV000281096	pathogenic	not provided	2015-01-30	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000223984	SCV000338139	pathogenic	not provided	2015-12-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000778741	SCV000915099	pathogenic	Fraser syndrome 1	2024-06-11	criteria provided, single submitter	clinical testing
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000778741	SCV002505836	pathogenic	Fraser syndrome 1	2021-08-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000223984	SCV003525850	pathogenic	not provided	2023-11-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr2517*) in the FRAS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FRAS1 are known to be pathogenic (PMID: 12766769, 18671281). This variant is present in population databases (rs745597204, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with Fraser syndrome (PMID: 18671281). ClinVar contains an entry for this variant (Variation ID: 235484). For these reasons, this variant has been classified as Pathogenic.
Sydney Genome Diagnostics, Children's Hospital Westmead	RCV001328302	SCV001449324	pathogenic	Congenital anomaly of kidney and urinary tract	2018-11-22	no assertion criteria provided	clinical testing	This individual is heterozygous for the c.7551T>A variant in the FRAS1 gene. This variant creates a premature stop codon p.(Tyr2517*) and may result in a null allele due to nonsense-mediated mRNA decay. This variant has been reported in the gnomAD browser (http://gnomad.broadinstitute.org) with a very low allele frequency of 0.002% (5 out of 244, 500 alleles). The variant has been previously reported in a patient with Fraser syndrome (Haelst et al Am J Med Genet A. 2008 Sep 1;146A(17):2252-2257) and has also been listed on ClinVar to be pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/235484/). This variant is considered to be a pathogenic according to the ACMG guidelines. (Evidence used: PVS1, PM2, PP5).