ClinVar Miner

Submissions for variant NM_000038.6(APC):c.531+5_531+8del (rs1554071617)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000646455 SCV000768227 likely pathogenic Familial adenomatous polyposis 1 2018-01-11 criteria provided, single submitter clinical testing This sequence change falls in intron 5 of the APC gene. It does not directly change the encoded amino acid sequence of the APC protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with familial adenomatous polyposis (PMID: 15459959). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this intronic change can result in skipping of exon 4 of the APC mRNA (PMID: 15459959). A different variant that affects the +5 position of intron 5 of APC gene in the same way as this variant (c.531+5G>C) has been determined to be pathogenic (PMID: 19196998, 12010888). This suggests that the +5 position in this intron is important for normal RNA splicing, and that other variants that affect this position may also be pathogenic. 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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