Submissions for variant NM_001110792.2(MECP2):c.90C>G (p.Leu30=)

gnomAD frequency: 0.00006  dbSNP: rs372500343

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV003235098	SCV003934950	benign	Rett syndrome	2023-06-15	reviewed by expert panel	curation	The allele frequency of the c.54C>G p.Leu18= variant in MECP2 (NM_004992.1) is 0.042% in the African/African American sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). The silent p.Leu18= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP4, BP7). In summary, the c.54C>G p.Leu18= variant in MECP2 is classified as Benign based on the ACMG/AMP criteria (BA1, BP4, BP7).
Eurofins Ntd Llc (ga)	RCV000724858	SCV000229063	uncertain significance	not provided	2015-05-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000724858	SCV000728699	likely benign	not provided	2020-06-23	criteria provided, single submitter	clinical testing
Invitae	RCV001499199	SCV001703957	likely benign	Severe neonatal-onset encephalopathy with microcephaly	2023-08-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003895193	SCV004715844	likely benign	MECP2-related condition	2023-08-24	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).