ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
22241717 SDHAF2 (also known SDH5) is a tumor suppressor gene which encodes for a protein required for flavination of a succinate dehydrogenase subunit. A novel frameshift mutation was reported by Piccini et al 2012 (PMID: 22241717) in a 44-year-old woman diagnosed with paraganglioma, but with a negative family history. In exon 4, she had c.357-358insT (p.Tyr119LeufsX7) mutation which has not been observed in other patients and there was no indication that other family members were tested.
26096992 Zhu et al 2015 (PMID 26096992) assessed the frequency of germline mutations in Chinese patients with head and neck paragangliomas (HNPGL) without family history. They identified one female patient who had early age of onset of HNPGL who had a novel truncation mutation c.130C>T (p.Gln44Ter).

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.