rs139717960

Description

This variant is associated with the following publications: (PMID: 24429398, 18220287, 15146463, 22995991, 24123792, 26489027, 9361030, 29966037)

The p.Ser487Leu variant in EYA1 is classified as likely benign because it is present in 0.13% (177/129002) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has been reported in 1 individual with Branchio-oto-renal syndrome, 2 individuals with hearing loss, and 4 individuals with vesicouretal reflux/CAKUT (Chang 2004, Neveling 2013, Hwang 2014, Nicolaou 2016). It has also been identified in 1 individual with ear abnormalities and hypoplastic kidneys who also had a 2q23 microdeletion and a de novo pathogenic variant in the CHD7 gene; the p.Ser487Leu variant segregated in the father with branchial cyst and duplication of renal collecting system (Badilla-Porras 2012). This variant has been reported by our laboratory in 2 unrelated Caucasian individuals with sensorineural hearing loss due to alternate genetic etiologies as well as in an unaffected parent. In summary, the frequency data and identification of this variant in individuals with an alternate genetic etiology and unaffected parent support a likely benign classification, despite the reports in the literature. ACMG/AMP Criteria applied: BA1, BS2_Supporting, BP5, PS4_Supporting.

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.