Submissions for variant NM_001110792.2(MECP2):c.855G>T (p.Gly285=)

gnomAD frequency: 0.00046  dbSNP: rs61750245

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Molecular Genetics Laboratory, Children's Mercy Hospital and Clinics	RCV000172862	SCV000223844	benign	Rett syndrome		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000172862	SCV000282498	benign	Rett syndrome	2015-12-01	criteria provided, single submitter	clinical testing	The variant of interest causes a synonymous change with 3/5 in silico programs predicting no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest was observed in a large, broad control population, ExAC, with an allele frequency of 48/85990 (1/1791 including 18 hemizygotes), which exceeds the maximum expected allele frequency for a pathogenic MECP2 variant. The variant of interest has been reported in affected individuals via publications and reputable clinical laboratories/databases with a classification of "benign/polymorphism." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Benign.
Invitae	RCV001079813	SCV000645678	benign	Severe neonatal-onset encephalopathy with microcephaly	2024-02-01	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000712286	SCV000842738	benign	not provided	2018-07-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002426696	SCV002681375	benign	Inborn genetic diseases	2017-07-27	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Centre for Population Genomics, CPG	RCV000172862	SCV004098840	benign	Rett syndrome	2023-08-14	criteria provided, single submitter	curation	This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria.Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 2.0, this variant is classified as Benign. At least the following criteria are met: The allele frequency of this variant in at least one population in gnomAD is higher than the 0.03% threshold defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders VCEP 2.0 (BA1).
PreventionGenetics, part of Exact Sciences	RCV003965081	SCV004780228	benign	MECP2-related condition	2021-03-22	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
RettBASE	RCV000133248	SCV000188252	benign	not specified	2013-12-05	no assertion criteria provided	curation
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000133248	SCV001953862	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000712286	SCV001974958	likely benign	not provided		no assertion criteria provided	clinical testing