ClinGen Dosage Sensitivity Curation Page

EYA1

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
30086703 In 2018, Wang et al. used PCR and Sanger sequencing on a family with Branchio-oto-renal (BOR) syndrome to identify potential variants in EYA1. Analysis identified a nonsense variant (p. Arg323X) in EYA1 in the proband and 3 affected family members. Of note, this variant was not present in the unaffected family members.
16813606 In 2006, Clarke et al. used PCR on a family with Branchio-oto-renal (BOR) syndrome and Branchiootic (BO) syndrome to identify potential variants in EYA1. Analysis identified a variant resulting in a premature stop codon and potential protein truncation in the affected father and son. Of note, the father also had a child with bilaterally absent kidneys who is deceased, and thus was not available for this study. Testing revealed that the variant was de novo to the father, as it was not present in his parents. The variant was absent in all unaffected family members. Additionally, a missense variant was also identified in 1 of the affected individuals, but this variant was also present in unaffected family members.
29552445 In 2018, Lie et al. used PCR and direct sequencing on an individual with Branchio-oto-renal (BOR) syndrome to investigate EYA1. Analysis identified a frameshift variant (p.R461fs467X) in EYA1 which leads to protein truncation. This variant was de novo, as it was not present in the proband?s unaffected parents.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.