Submissions for variant NM_006231.4(POLE):c.2865-5_2865-4del

dbSNP: rs369732588

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000662925	SCV000785873	benign	Colorectal cancer, susceptibility to, 12	2017-12-21	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV001701149	SCV002568045	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002499141	SCV002805622	likely benign	Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome; Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency	2021-09-23	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356345	SCV001551489	uncertain significance	Carcinoma of colon		no assertion criteria provided	clinical testing	The POLE c.2865-5_2865-4delTT variant was not identified in the literature nor was it identified in the ClinVar or MutDB databases. The variant was identified in dbSNP (ID: rs767764560) as "NA", and the Cosmic database (1x, confirmed somatic, in melanoma of the eye). The variant was not identified in the control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.2865-5_2865-4delTT variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579561	SCV001807692	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001701149	SCV001917919	benign	not specified		no assertion criteria provided	clinical testing