Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Pittsburgh Clinical Genomics Laboratory, |
RCV004784963 | SCV005397253 | likely pathogenic | Hereditary cryohydrocytosis with reduced stomatin | 2022-05-09 | criteria provided, single submitter | clinical testing | This sequence variant is a single nucleotide substitution (C>A) at the -12 position upstream of exon 6 of the SLC2A1 gene. This is a novel variant which has not been reported in clinical genetics databases or observed in the medical literature in individuals with SLC2A1-related disease, to our knowledge. This variant is absent from the gnomAD control population dataset (0/282818 alleles). This variant is predicted to create a new splice acceptor site with greater efficiency than the tural exon 6 splice acceptor site. Use of this new splicing acceptor would result in a frameshift due to an insertion of 10 nucleotides (insGTCCCCCAG) at the beginning of the exon 6 sequence. However, this prediction has not been confirmed with in vitro or in vivo splicing assays, to our knowledge. This variant was not detected by NGS in either parent. Based on the current evidence, we consider this variant to be likely pathogenic. ACMG Criteria: PM2, PP3, PS2 |