ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1312+3A>G (rs863225311)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000490831 SCV000579815 likely pathogenic Hereditary cancer-predisposing syndrome 2018-04-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Functionally-validated splicing mutation
Counsyl RCV000204247 SCV000677777 likely pathogenic Familial adenomatous polyposis 1 2017-02-16 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000500343 SCV000591068 pathogenic Familial adenomatous polyposis criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000202161 SCV000333807 likely pathogenic not provided 2015-09-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763540 SCV000894353 likely pathogenic Desmoid disease, hereditary; Carcinoma of colon; Familial adenomatous polyposis 1; Neoplasm of stomach; Hepatocellular carcinoma 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000202161 SCV000565782 pathogenic not provided 2017-05-15 criteria provided, single submitter clinical testing This variant is denoted APC c.1312+3A>G or IVS10+3A>G and consists of an A>G nucleotide substitution at the +3 position of intron 10 of the APC gene. This variant, also reported as APC IVS9+3A>G using alternate nomenclature, has been observed in multiple individuals with a personal and/or family history of polyposis (Olschwang 1993, Aretz 2004, Friedl 2005, Nielsen 2007, Filipe 2009, Kaufmann 2009, Lagarde 2010, Kerr 2013). Multiple in silico models predict this variant to damage the nearby natural splice donor site. In addition, mRNA analysis has identified that this variant results in partial skipping of exon 9 (Aretz 2004). Based on the current evidence, we consider this variant to be pathogenic.
Invitae RCV000204247 SCV000261158 pathogenic Familial adenomatous polyposis 1 2018-12-18 criteria provided, single submitter clinical testing This sequence change falls in intron 10 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 many individuals affected with familial adenomatous polyposis (FAP), and has been found to segregate with disease in at least one family (PMID: 8381580, 20685668, 15459959, 23159591, 24599579, Invitae). ClinVar contains an entry for this variant (Variation ID: 217924). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant leads to partial skipping of exon 9 (PMID: 15459959). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202161 SCV000256916 pathogenic not provided no assertion criteria provided research

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