ClinVar Miner

Submissions for variant NM_000038.6(APC):c.220+2T>A (rs587781809)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130080 SCV000184907 likely pathogenic Hereditary cancer-predisposing syndrome 2017-07-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Color RCV000130080 SCV000686880 likely pathogenic Hereditary cancer-predisposing syndrome 2018-07-12 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000503701 SCV000591018 pathogenic Familial adenomatous polyposis 2015-11-20 criteria provided, single submitter clinical testing
GeneDx RCV000202191 SCV000322198 likely pathogenic not provided 2017-03-09 criteria provided, single submitter clinical testing This variant is denoted APC c.220+2T>A or IVS3+2T>A and consists of a T>A nucleotide substitution at the +2 position of intron 3 of the APC gene. This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been identified in an individual undergoing APC analysis and was classified as pathogenic (Kerr 2013). Based on currently available information, we consider APC c.220+2T>A to be a likely pathogenic variant.
Invitae RCV000231290 SCV000282713 likely pathogenic Familial adenomatous polyposis 1 2018-12-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the APC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has been reported in the literature in an individual being evaluated for familial adenomatous polyposis (PMID: 23159591). ClinVar contains an entry for this variant (Variation ID: 141515). 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. 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). 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.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202191 SCV000256945 likely pathogenic not provided no assertion criteria provided research
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000202191 SCV000600057 likely pathogenic not provided 2016-11-04 criteria provided, single submitter clinical testing

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