Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
MVZ Dr. |
RCV001290767 | SCV001478899 | pathogenic | Hereditary spherocytosis | 2020-03-17 | criteria provided, single submitter | clinical testing | The variant c.6788+11C>T is at low frequency in ensembl and gnomAD (2.1: 4 of 248534 alleles). Multiple lines of computational evidence support a deleterious effect on the gene or gene product. Splice algorithms (SpliceSiteFinder-like, NNSplice, GeneSplicer) recognize a new donor site with higher score than the native donor site. If this new splice donor site would be used 9 nucleotides of the intron will remain within the mRNA and lead to a premature stop codon. Further RNA analysis in our laboratory showed alternatively spliced mRNA with the predicted additional 9 nucleotides from intron 48 and the premature stop codon. Therefore this nonsense mutation is a null variant in a gene where loss of function is a known mechanism of disease and was classified a pathogenic. |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV003234029 | SCV003932278 | pathogenic | Hereditary spherocytosis type 3 | 2023-01-31 | criteria provided, single submitter | clinical testing | PM2, PM3, PS3_Very Strong |