ClinVar Miner

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

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
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 The c.286+2T>A intronic pathogenic mutation results from a T to A substitution two nucleotides after coding exon 3 in the SDHB gene. This mutation has been detected in an individual with a malignant paraganglioma (PGL) (Brouwers FM et al. J. Clin. Endocrinol. Metab. 2006 Nov;91:4505-9), a 37 year old male diagnosed with renal cell carcinoma (Ricketts CJ et al. J. Urol. 2012 Dec;188:2063-71), and in an 18 year old male who was diagnosed with a PGL whose father reportedly had a head and neck PGL (Ghayee HK et al. Endocr. Relat. Cancer. 2009 Mar;16:291-9). Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
Invitae RCV000475161 SCV000554021 pathogenic Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-02-05 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 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); Observed in individuals with SDHB-related tumors (Brouwers 2006, Ghayee 2009, Ricketts 2012, Ben Aim 2019, Bayley 2020); This variant is associated with the following publications: (PMID: 25525159, 19075037, 16912137, 30877234, 23083876, 31492822, 28152038, 28409892, 31579262, 32741965)
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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.