Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001379490 | SCV001577302 | pathogenic | Hereditary pheochromocytoma-paraganglioma | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 1 of the SDHAF2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SDHAF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1068054). Studies have shown that disruption of this splice site results in skipping of exons 2-3 and skipping of exon 2 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002357285 | SCV002624610 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-07-11 | criteria provided, single submitter | clinical testing | The c.37-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 2 in the SDHAF2 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |