ClinVar Genomic variation as it relates to human health

Variant summary: The variant involves the deletion of exon 3 in the SDHB gene. A presumed nomenclature of c.(200+1_201-1)_(286+1_287-1)del has been designated for the purposes of this classification. This Copy Number Variant (CNV) is expected to alter the reading frame and predicted to result in a truncation or absence of the encoded protein due to nonsense mediated decay (NMD). The variant allele was found at a frequency of 8.3e-06 in 120780 control chromosomes in the gnomAD database (Structural Variants v4.0 dataset). The deletion of exon 3 in the SDHB gene has been reported in the literature in multiple individuals affected with Hereditary Paraganglioma-Pheochromocytoma Syndrome, and a large 7.9-kb deletion encompassing exon 3 of the SDHB gene is also known in the literature as the Dutch founder exon 3 deletion (e.g. Bayley_2009, Gordon_2022). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 528762). Based on the evidence outlined above, the variant was classified as pathogenic.