Submissions for variant NM_018972.4(GDAP1):c.695-9T>A (rs906225606)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000523643	SCV000616732	uncertain significance	not provided	2018-07-10	criteria provided, single submitter	clinical testing	The c.695-9T>A variant in the GDAP1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant reduces the quality of the splice acceptor site in intron 5, and is expected to cause abnormal gene splicing. This substitution occurs at a position that is conserved in mammals. The c.695-9T>A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.695-9T>A as a variant of uncertain significance.
Invitae	RCV000690588	SCV000818278	uncertain significance	Charcot-Marie-Tooth disease, type 4A	2019-03-15	criteria provided, single submitter	clinical testing	This sequence change falls in intron 5 of the GDAP1 gene. It does not directly change the encoded amino acid sequence of the GDAP1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GDAP1-related disease. ClinVar contains an entry for this variant (Variation ID: 449029). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.