Submissions for variant NM_000503.6(EYA1):c.299C>A (p.Thr100Asn)

gnomAD frequency: 0.00005  dbSNP: rs373501480

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000156019	SCV000205731	uncertain significance	not specified	2013-08-19	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Thr100Asn varia nt in EYA1 has not been previously reported in individuals with hearing loss, bu t has been identified in 0.02% (1/4406) of African American chromosomes by the N HLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs373501 480). This frequency is not high enough to rule out pathogenicity. The threonin e (Thr) residue at position 100 is not completely conserved across species, with platypus and frog having an asparagine (Asn) at this position. In summary, addi tional information is needed to determine the clinical significance of this vari ant; however, we would lean towards a more likely benign role.
Illumina Laboratory Services, Illumina	RCV000371539	SCV000474867	uncertain significance	Branchiootic syndrome 1	2018-01-13	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000281370	SCV000474868	likely benign	Otofaciocervical syndrome 1	2018-01-13	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
PreventionGenetics, part of Exact Sciences	RCV003407581	SCV004107053	uncertain significance	EYA1-related condition	2023-08-29	criteria provided, single submitter	clinical testing	The EYA1 c.299C>A variant is predicted to result in the amino acid substitution p.Thr100Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0080% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-72234088-G-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.