Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV001262451 | SCV001440330 | likely pathogenic | Paragangliomas 2 | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004659450 | SCV005161186 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-05-09 | criteria provided, single submitter | clinical testing | The c.42_45delTGCT variant, located in coding exon 2 of the SDHAF2 gene, results from a deletion of 4 nucleotides at nucleotide positions 42 to 45, causing a translational frameshift with a predicted alternate stop codon (p.A15Cfs*13). The predicted stop codon occurs in the 5’ end of theSDHAF2 gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNAdecay and/or lead to re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). Direct evidence for this alteration is unavailable, however premature termination codons are typically deleterious in nature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |