Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV001089579 | SCV001244814 | pathogenic | Usher syndrome type 2A | 2018-05-29 | criteria provided, single submitter | clinical testing | A heterozygous nonsense variant, NM_206933.2(USH2A):c.10699delC, has been identified in exon 54 of 72 of the USH2A gene. The variant is predicted to result in a premature stop codon at position 3567 of the protein (NP_996816.2(USH2A):p.(Leu3567*)). This variant is predicted to result in loss of protein function either through truncation (including the loss of multiple domains) or nonsense-mediated decay. The variant is absent in population databases (gnomAD). It has not been previously reported in clinical cases however, multiple truncating variants (upstream and downstream) have previously been reported as pathogenic (ClinVar). Based on the information available at the time of curation and in conjunction with the c.2299delG variant, this variant has been classified as PATHOGENIC.NB: This variant has been reclassified as pathogenic due to confirmed compound heterozygous inheritance, consistent with Usher syndrome. |
Invitae | RCV001389327 | SCV001590652 | pathogenic | not provided | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu3567*) in the USH2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with deafness, inherited retinal degeneration, autosomal recessive retinitis pigmentosa and/or Usher syndrome (PMID: 30073356, 31827275, 32037395, 33576794). ClinVar contains an entry for this variant (Variation ID: 869481). For these reasons, this variant has been classified as Pathogenic. |
DBGen Ocular Genomics | RCV001593259 | SCV001816034 | pathogenic | Retinitis pigmentosa 39 | 2021-06-28 | criteria provided, single submitter | clinical testing | |
DBGen Ocular Genomics | RCV001089579 | SCV004101729 | pathogenic | Usher syndrome type 2A | 2020-01-01 | criteria provided, single submitter | clinical testing | Class 5 ACMG Guidelines, 2015 |
Genome- |
RCV001593259 | SCV004182189 | pathogenic | Retinitis pigmentosa 39 | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001089579 | SCV004182190 | pathogenic | Usher syndrome type 2A | 2023-11-04 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001089579 | SCV002088350 | pathogenic | Usher syndrome type 2A | 2020-08-10 | no assertion criteria provided | clinical testing |