Submissions for variant NM_017841.4(SDHAF2):c.98G>A (p.Arg33His)

gnomAD frequency: 0.00002  dbSNP: rs777442412

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000639349	SCV000760921	uncertain significance	Hereditary pheochromocytoma-paraganglioma	2024-07-30	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 33 of the SDHAF2 protein (p.Arg33His). This variant is present in population databases (rs777442412, gnomAD 0.003%). 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: 532518). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001579475	SCV002011574	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002386044	SCV002690985	uncertain significance	Hereditary cancer-predisposing syndrome	2023-09-12	criteria provided, single submitter	clinical testing	The p.R33H variant (also known as c.98G>A), located in coding exon 2 of the SDHAF2 gene, results from a G to A substitution at nucleotide position 98. The arginine at codon 33 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV005231214	SCV005872571	uncertain significance	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579475	SCV001807402	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001579475	SCV001955572	likely benign	not provided		no assertion criteria provided	clinical testing