ClinVar Miner

Submissions for variant NM_017841.4(SDHAF2):c.37-1G>C (rs761956866)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000994638 SCV001148296 likely pathogenic not provided 2017-01-01 criteria provided, single submitter clinical testing
Invitae RCV001238114 SCV001410911 likely pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes 2020-06-07 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 1 of the SDHAF2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHAF2-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SDHAF2 are known to be pathogenic (PMID: 22241717, 26096992). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV000994638 SCV001770055 likely pathogenic not provided 2021-04-15 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease Not observed in large population cohorts (Lek et al., 2016) Has not been previously published as pathogenic or benign to our knowledge

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