ClinVar Miner

Submissions for variant NM_016169.4(SUFU):c.183-1G>A

dbSNP: rs1554841447
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000628498 SCV000749400 likely pathogenic Gorlin syndrome; Medulloblastoma 2022-11-09 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 1 of the SUFU gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SUFU are known to be pathogenic (PMID: 22508808, 25403219, 33024317). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SUFU-related conditions. ClinVar contains an entry for this variant (Variation ID: 524654). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Ambry Genetics RCV004948478 SCV005513077 uncertain significance Hereditary cancer-predisposing syndrome 2024-08-07 criteria provided, single submitter clinical testing The c.183-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 2 of the SUFU 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 acceptor site and will result in the creation or strengthening of a novel splice acceptor site. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNA decay; however, direct evidence is insufficient at this time. The exact functional effect of the altered amino acid sequence is unknown. Based on the available evidence, the clinical significance of this variant remains unclear.

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