ClinVar Miner

Submissions for variant NM_017841.4(SDHAF2):c.370+3A>G

gnomAD frequency: 0.00001  dbSNP: rs773940746
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001349765 SCV001544125 uncertain significance Hereditary pheochromocytoma-paraganglioma 2020-10-05 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the SDHAF2 gene. It does not directly change the encoded amino acid sequence of the SDHAF2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs773940746, ExAC 0.002%). This variant has not been reported in the literature in individuals with SDHAF2-related conditions. 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 RCV004036594 SCV005027576 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-27 criteria provided, single submitter clinical testing The c.370+3A>G intronic variant results from an A to G substitution 3 nucleotides after coding exon 3 in the SDHAF2 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Based on the available evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004570852 SCV005056613 uncertain significance Paragangliomas 2 2024-01-17 criteria provided, single submitter clinical testing

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