Submissions for variant NM_000038.6(APC):c.136-2A>G

dbSNP: rs886039625

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000254746	SCV000322549	pathogenic	not provided	2018-04-12	criteria provided, single submitter	clinical testing	This variant is denoted APC c.136-2A>G or IVS2-2A>G and consists of an A>G nucleotide substitution at the -2 position of intron 2 of the APC gene. This variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing, leading to an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has not, to our knowledge, been published in the literature. Based on the current evidence, we consider this variant to be pathogenic.
Invitae	RCV002518766	SCV001229485	likely pathogenic	Familial adenomatous polyposis 1	2020-04-16	criteria provided, single submitter	clinical testing	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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). 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. This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 265561). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 2 of the APC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.