ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.642+2T>G (rs1553177424)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519924 SCV000616873 pathogenic not provided 2015-08-04 criteria provided, single submitter clinical testing The c.642+2 T>G splice site mutation in the SDHB gene destroys the canonical splice donor site in intron 6. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.642+2 T>G mutation 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.
Invitae RCV001207024 SCV001378361 likely pathogenic Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2019-07-15 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 6 of the SDHB 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 SDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 449099). 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 SDHB are known to be pathogenic (PMID: 19454582, 19802898). 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.

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