ClinVar Miner

Submissions for variant NM_000038.6(APC):c.-30418_-30417delinsTAGCAAGGG

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000808449 SCV000948558 likely pathogenic Familial adenomatous polyposis 1 2018-11-20 criteria provided, single submitter clinical testing This variant occurs in a non-coding region of the APC gene. It does not change the encoded amino acid sequence of the APC protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed in an individual with clinical features consistent with familial adenomatous polyposis (Invitae). While experimental studies and prediction algorithms are not available for this variant, it disrupts a region of the APC promoter that has been proposed to include the DNA binding site for the YY1 transcription factor. Other variants that affect this region of the APC promoter (c.-30416G>A, c.-30417T>C, c.-30418A>G, and c.-30418A>T) have been shown to disrupt YY1 binding to the APC promoter and result in reduced APC expression (PMID: 20685668, 21813476, 27087319). Other variants that disrupt the DNA sequence in this region of the APC promoter have been observed in affected individuals (PMID: 20685668, 21813476, 27087319, 27343414, Invitae), suggesting that integrity of this region is clinically significant. As a result, variants that disrupt this region of the APC promoter are likely to be causative of disease. 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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