Submissions for variant NM_000038.6(APC):c.3249T>G (p.Asp1083Glu) (rs201629780)

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129075	SCV000183778	benign	Hereditary cancer-predisposing syndrome	2015-11-27	criteria provided, single submitter	clinical testing
Invitae	RCV000204842	SCV000261248	benign	Familial adenomatous polyposis 1	2017-12-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000236472	SCV000292453	likely benign	not specified	2017-08-02	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV000236472	SCV000591136	likely benign	not specified	2012-11-26	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	RCV000034410	SCV000694028	benign	not provided	2016-05-16	criteria provided, single submitter	clinical testing	Variant summary: The APC c.3249T>G (p.Asp1083Glu) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). It does not lie in a known MCR (mutation cluster region) located at exon 15 where pathogenic variants are clustered (PMIDs 1338904 and 18387968). This variant was found in 17/121710 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0002413 (16/66310). This frequency is about 3 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. In a FAP family reported in literature, it was found in affected as well as unaffected members suggesting that it is unlikely to cause disease in the family (Gayther_1995). In addition, it was also found to co-occur with another pathogenic variant c.1312+3A>G in one sample reported n UMD database, further supporting a benign outcome. A diagnostic center and a reputable database have classified this variant as likely benign/benign. Taken together, this variant has been classified as Benign.
PreventionGenetics,PreventionGenetics	RCV000034410	SCV000805391	likely benign	not provided	2017-05-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000034410	SCV000887519	benign	not provided	2018-02-21	criteria provided, single submitter	clinical testing
Color	RCV000129075	SCV000910614	benign	Hereditary cancer-predisposing syndrome	2016-06-19	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health	RCV000034410	SCV000043119	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.