Submissions for variant NM_000503.6(EYA1):c.35G>A (p.Arg12His)

gnomAD frequency: 0.00035  dbSNP: rs74720958

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000825672	SCV000967090	benign	not specified	2018-09-13	criteria provided, single submitter	clinical testing	The p.Arg12His variant in EYA1 is classified as benign because it has been ident ified in 0.07% (14/18868) of East Asian chromosomes and 0.03% (38/126718) of Eur opean chromosomes, including one homozygote, by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). Furthermore, arginine (Arg) at posit ion 12 is not conserved in mammals or evolutionarily distant species and 3 mamma ls (chinchilla, brush-tailed rat, and pig) carry a histidine (His) at this posit ion. ACMG/AMP Criteria applied: BS1, BP4_Strong.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001198098	SCV001368899	uncertain significance	Otofaciocervical syndrome 1	2019-02-25	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3.
Invitae	RCV002067414	SCV002324623	benign	Melnick-Fraser syndrome	2021-10-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003975339	SCV004788040	likely benign	EYA1-related condition	2023-05-31	criteria provided, single submitter	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).