Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001047946 | SCV001211932 | uncertain significance | Leber congenital amaurosis 3 | 2022-08-09 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the SPATA7 mRNA. The next in-frame methionine is located at codon 52. This variant is present in population databases (rs200244203, gnomAD 0.01%). Disruption of the initiator codon has been observed in individual(s) with retinitis pigmentosa (PMID: 22334370). ClinVar contains an entry for this variant (Variation ID: 844972). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Institute of Medical Genetics and Applied Genomics, |
RCV001291572 | SCV001480107 | likely pathogenic | not provided | 2021-02-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003117722 | SCV003801149 | likely pathogenic | Leber congenital amaurosis | 2023-01-07 | criteria provided, single submitter | clinical testing | Variant summary: SPATA7 c.3G>A (p.Met1Ile) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. An alternative downstream in-frame start codon (Met52) is located in exon 3 of the encoded protein. Other presumably pathogenic truncating variants have been reported upstream of this alternate codon in the HGMD database (example, c.20_21delTC, p.Val7Glufs*16). Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.7e-05 in 233902 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in SPATA7 causing Leber Congenital Amaurosis (4.7e-05 vs 0.00087), allowing no conclusion about variant significance. c.3G>A has been reported in the literature in at least one compound heterozygous individual affected with Retinitis Pigmentosa (Neveling_2012). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic and one as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001291572 | SCV001956827 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001291572 | SCV001974080 | pathogenic | not provided | no assertion criteria provided | clinical testing |