Submissions for variant NM_000503.6(EYA1):c.890G>A (p.Arg297Gln)

gnomAD frequency: 0.00007  dbSNP: rs148647933

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000326184	SCV000474843	benign	Branchiootic syndrome 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000380843	SCV000474844	benign	Otofaciocervical syndrome 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000610919	SCV000711026	uncertain significance	not specified	2016-05-21	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Arg297Gln var iant in EYA1 has not been previously reported in individuals with hearing loss, but has been identified in 0.2% (17/8654) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs148647933 ). Computational prediction tools and conservation analyses do not provide stron g support for or against an impact to the protein. In summary, while the clinica l significance of the p.Arg297Gln variant is uncertain, its frequency in the ExA C database suggests that it is more likely to be benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002524575	SCV001018772	likely benign	Melnick-Fraser syndrome	2024-11-27	criteria provided, single submitter	clinical testing
GeneDx	RCV002221531	SCV002498821	likely benign	not provided	2023-05-03	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
PreventionGenetics, part of Exact Sciences	RCV003932507	SCV004753913	likely benign	EYA1-related disorder	2021-07-26	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).