Submissions for variant NM_017841.4(SDHAF2):c.32C>A (p.Ser11Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003069774	SCV003469937	pathogenic	Hereditary pheochromocytoma-paraganglioma	2022-11-05	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SDHAF2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser11*) in the SDHAF2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDHAF2 are known to be pathogenic (PMID: 22241717, 26096992).
Ambry Genetics	RCV004071868	SCV005027430	uncertain significance	Hereditary cancer-predisposing syndrome	2023-11-30	criteria provided, single submitter	clinical testing	The p.S11* variant (also known as c.32C>A), located in coding exon 1 of the SDHAF2 gene, results from a C to A substitution at nucleotide position 32. This changes the amino acid from a serine to a stop codon within coding exon 1. 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). The exact functional effect of this alteration is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.