Submissions for variant NM_001939.3(DRP2):c.1006C>T (p.Gln336Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002885436	SCV003239293	pathogenic	not provided	2022-10-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with DRP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln336*) in the DRP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DRP2 are known to be pathogenic (PMID: 22764250, 26227883).
PreventionGenetics, part of Exact Sciences	RCV003409945	SCV004111843	uncertain significance	DRP2-related disorder	2023-02-27	criteria provided, single submitter	clinical testing	The DRP2 c.1006C>T variant is predicted to result in premature protein termination (p.Gln336*). To our knowledge, this variant has not been reported in the literature. This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. However, truncating variants in DRP2 have been reported in individuals with Charcot-Marie-Tooth disease phenotypes (see, for example, Brennan et al. 2015. PubMed ID: 26227883). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.