Submissions for variant NM_001110792.2(MECP2):c.6CGC[4] (p.Ala7_Ala8del)

dbSNP: rs398123566

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV002260623	SCV002540682	uncertain significance	Rett syndrome	2022-04-28	reviewed by expert panel	curation	The p.Ala7_Ala8del variant in MECP2 (NM_001110792.2) is present in 1 male individual in gnomAD (0.006%) (not sufficient to meet BS1 criteria). Larger deletions encompassing this region (p.Ala6_Ala8del) have been observed in an unaffected mother and father (Invitae internal database) (BP3). This variant has been observed in an individual with neurodevelopment disorder (PMID 1717659) (not sufficient for PS4_supporting). The p.Ala7_Ala8del variant is not present in additional databases (internal and publicly available), therefore, no additional criteria are applicable at this time. In summary, the p.Ala7_Ala8del variant in MECP2 is classified as a variant of unknown significance based on the ACMG/AMP criteria (BP3).
GeneDx	RCV000144800	SCV000191025	likely benign	not specified	2017-10-27	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000701456	SCV000830257	likely benign	Severe neonatal-onset encephalopathy with microcephaly	2025-01-19	criteria provided, single submitter	clinical testing
Centre for Population Genomics, CPG	RCV002260623	SCV004232234	benign	Rett syndrome	2024-01-16	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 3.0, 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 between 0.008% and 0.03% (BS1). The variant is observed in at least 2 individuals with no features of Rett Syndrome (BS2).
RettBASE	RCV000170277	SCV000222609	uncertain significance	X-linked intellectual disability-psychosis-macroorchidism syndrome	2007-11-01	no assertion criteria provided	curation
PreventionGenetics, part of Exact Sciences	RCV004734698	SCV005351908	uncertain significance	MECP2-related disorder	2024-03-26	no assertion criteria provided	clinical testing	The MECP2 c.18_23del6 variant is predicted to result in an in-frame deletion (p.Ala7_Ala8del). This variant has been reported in an individual with intellectual disability (Harvey et al. 2007. PubMed ID: 17171659). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.