ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.286+2T>A (rs587781270)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000128905 SCV000172772 pathogenic Hereditary cancer-predisposing syndrome 2016-11-23 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000475161 SCV000554021 pathogenic Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2019-12-26 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the SDHB gene. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product. Donor and acceptor splice site variants are typically truncating (PMID: 16199547), and truncating variants in SDHB are known to be pathogenic (PMID: 19802898, 19454582). This variant has been reported in an individual affected with malignant paraganglioma (PMID: 16912137), and an individual with renal cell carcinoma (PMID: 23083876). ClinVar contains an entry for this variant (Variation ID: 140773). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000481752 SCV000567709 pathogenic not provided 2015-08-19 criteria provided, single submitter clinical testing The c.286+2 T>A variant in the SDHB gene has previously been reported in association with paraganglioma and renal cell cancer (Brouwers et al., 2006; Ghayee et al., 2009; Ricketts et al., 2012). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant destroys the canonical splice donor site in intron 3, and is expected to cause abnormal gene splicing. Therefore, the c.286+2 T>A variant is considered pathogenic.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000660254 SCV000782273 pathogenic Paragangliomas 4 2016-11-01 criteria provided, single submitter clinical testing
Section on Medical Neuroendocrinolgy,National Institutes of Health RCV000505293 SCV000599492 likely pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes no assertion criteria provided research

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