ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.1435-2A>C

dbSNP: rs1553123105
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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 RCV000819095 SCV000959738 uncertain significance Familial adenomatous polyposis 2 2024-01-03 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 15 of the MUTYH gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 661635). Variants that disrupt 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. 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 RCV001011885 SCV001172265 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-20 criteria provided, single submitter clinical testing The c.1519-2A>C intronic variant results from an A to C substitution two nucleotides upstream from coding exon 16 in the MUTYH gene. This alteration occurs at the 3' terminus of the MUTYH gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last coding exon. The exact functional effect of this alteration is unknown. 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; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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