Submissions for variant NM_007289.4(MME):c.655-2A>G

gnomAD frequency: 0.00001  dbSNP: rs765591205

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV005090187	SCV005834230	pathogenic	not provided	2024-04-11	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 7 of the MME gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MME are known to be pathogenic (PMID: 26991897). This variant is present in population databases (rs765591205, gnomAD 0.06%). Disruption of this splice site has been observed in individual(s) with autosomal recessive Charcot-Marie-Tooth disease (PMID: 26991897). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 242841). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000234912	SCV000292059	pathogenic	Charcot-Marie-Tooth disease axonal type 2T	2016-07-06	no assertion criteria provided	literature only