Submissions for variant NM_001110792.2(MECP2):c.870C>T (p.Ala290=)

gnomAD frequency: 0.00041  dbSNP: rs61750248

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589640	SCV000698545	benign	not provided	2016-10-11	criteria provided, single submitter	clinical testing	Variant summary: The MECP2 c.834C>T (p.Ala278Ala) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts alterations to ESE binding, although these predictions have yet to be functionally assessed. The variant of interest has been observed in the large, broad control population, ExAC, with an allele frequency of 49/85676 (18 hemizygotes, 1/1748), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic MECP2 variant of 1/120481. In addition, multiple publications and a reputable database has cited the variant as "benign/silent polymorphism." Therefore, the variant of interest has been classified as Benign.
Ambry Genetics	RCV000716695	SCV000847538	likely benign	History of neurodevelopmental disorder	2016-08-23	criteria provided, single submitter	clinical testing	In silico models in agreement (benign);Synonymous alterations with insufficient evidence to classify as benign
Invitae	RCV001080240	SCV001003075	benign	Severe neonatal-onset encephalopathy with microcephaly	2024-01-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000589640	SCV001150512	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	MECP2: BP4, BP7, BS2
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589640	SCV001473251	benign	not provided	2020-03-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000589640	SCV001872490	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003952689	SCV004768434	likely benign	MECP2-related condition	2021-06-07	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).
RettBASE	RCV000168694	SCV000188255	benign	not specified	2010-03-10	no assertion criteria provided	curation
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000168694	SCV001932551	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000589640	SCV001975274	likely benign	not provided		no assertion criteria provided	clinical testing