ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.765+5G>A (rs199945904)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469261 SCV000554017 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-08-26 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the SDHB gene. It does not directly change the encoded amino acid sequence of the SDHB protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs199945904, ExAC 0.03%). This variant has been observed in an individual affected with paraganglioma and kidney cancer (Invitae). ClinVar contains an entry for this variant (Variation ID: 412480). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001026667 SCV001189096 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-24 criteria provided, single submitter clinical testing The c.765+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 7 in the SDHB gene. This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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