Submissions for variant NM_002692.4(POLE2):c.190C>T (p.Arg64Ter)

gnomAD frequency: 0.00001  dbSNP: rs765702439

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002016650	SCV002306371	uncertain significance	not provided	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg64*) in the POLE2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in POLE2 cause disease. This variant is present in population databases (rs765702439, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with POLE2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1511346). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.