Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000309264 | SCV000474831 | likely benign | Otofaciocervical syndrome 1 | 2017-04-28 | criteria provided, single submitter | clinical testing | 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. |
Illumina Laboratory Services, |
RCV000367199 | SCV000474832 | likely benign | Branchiootic syndrome 1 | 2017-04-28 | criteria provided, single submitter | clinical testing | 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Laboratory for Molecular Medicine, |
RCV000606853 | SCV000731974 | uncertain significance | not specified | 2017-09-25 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Gly426Ser (c.1276G>A) variant in EYA1 has been reported in one Japanese individual with c onductive hearing loss with additional clinical features of branchio-oto-renal s yndrome (Azuma 2000), and parental testing confirmed de novo occurrence of the v ariant in the individual. This variant has also been identified in 0.18% (33/188 60) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http:/ /gnomad.broadinstitute.org; dbSNP rs121909199); however this frequency is not hi gh enough to rule out a pathogenic role. The variant is also listed in ClinVar ( Variant ID 22977). Computational prediction tools and conservation analysis sugg est the variant may impact the protein. However, several in vitro functional stu dies provide conflicting data on the impact of the variant to normal protein fun ction (Buller 2001, Mutsuddi 2005, Rayapureddi 2006, Zou 2008, Li 2010, Ahmed 20 12, Patrick 2013, Musharraf 2014). It should be noted that in vitro studies may not accurately reflect biological function. In summary, while there is some sus picion for a pathogenic role, the clinical significance of the p.Gly426Ser varia nt is uncertain. |
Gene |
RCV000657911 | SCV000779677 | uncertain significance | not provided | 2022-12-02 | criteria provided, single submitter | clinical testing | Functional studies for this variant disagree on its effect; some indicate G426S or equivalent homologs reduce transcription level, affect optic development, and reduce interaction with Sox2 (Mutsuddi et al., 2005; Li et al., 2010; Zou et al., 2008), while others indicate G426S does not differ from wild-type (Ozaki et al., 2002; Musharraf et al., 2014); This variant is associated with the following publications: (PMID: 30221713, 29043394, 16797546, 11734542, 23435380, 10655545, 22340499, 24752894, 18678597, 19951260, 11950062, 24489909, 15802522, 35114279, 34868248) |
OMIM | RCV000008400 | SCV000028608 | pathogenic | Branchiootorenal syndrome with cataract | 2000-02-12 | no assertion criteria provided | literature only | |
Pediatric Nephrology |
RCV000496093 | SCV000584168 | benign | Branchiootorenal syndrome 1 | 2017-07-27 | no assertion criteria provided | clinical testing | Two cases without BOR syndrome possessed this variant. We conclude this is benign. |