Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002228020 | SCV000630898 | pathogenic | Melnick-Fraser syndrome | 2023-08-22 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 7943). This variant is also known as Arg328X. This premature translational stop signal has been observed in individual(s) with branchio-oto-renal syndrome (PMID: 16691597, 18177466, 21280147, 26969326). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg361*) in the EYA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EYA1 are known to be pathogenic (PMID: 10464653, 18220287). For these reasons, this variant has been classified as Pathogenic. |
| DASA | RCV000008406 | SCV002061219 | pathogenic | Branchiootorenal syndrome 1 | 2022-01-05 | criteria provided, single submitter | clinical testing | The c.1081C>T;p.(Arg361*) variant creates a premature translational stop signal in EYA1 gene. It is expected to result in an absent or disrupted protein product -PVS1.This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 7943; PMID: 26969326;18177466; 21280147) - PS4. This variant is not present in population databases (rs121909202, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic. |
| Gene |
RCV001823094 | SCV002072826 | pathogenic | not provided | 2022-09-21 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 18177466, 25525159, 26969326, 34387732, 31581539, 21280147, 16691597) |
| Ce |
RCV001823094 | SCV002545623 | pathogenic | not provided | 2022-06-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002512905 | SCV003564599 | pathogenic | Inborn genetic diseases | 2021-04-28 | criteria provided, single submitter | clinical testing | The c.1081C>T (p.R361*) alteration, located in exon 12 (coding exon 10) of the EYA1 gene, consists of a C to T substitution at nucleotide position 1081. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 361. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. The EYA1 c.1081C>T alteration was flagged as a low confidence call in the Genome Aggregation Database (gnomAD). This alteration has been reported in multiple patients with branchio-oto-renal (BOR) syndrome (Krug, 2011; Olavarrieta, 2008; Orten, 2008; Sloan-Heggen, 2016). Based on the available evidence, this alteration is classified as pathogenic. |
| OMIM | RCV000008405 | SCV000028613 | pathogenic | Branchiootic syndrome 1 | 2008-03-01 | no assertion criteria provided | literature only | |
| OMIM | RCV000008406 | SCV000028614 | pathogenic | Branchiootorenal syndrome 1 | 2008-03-01 | no assertion criteria provided | literature only |