ClinVar Miner

Submissions for variant NM_001110792.2(MECP2):c.-31AG[2]

dbSNP: rs587783128
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel RCV002260622 SCV002540698 benign Rett syndrome 2022-02-18 reviewed by expert panel curation The allele frequency of the c.-187_-186del variant in MECP2 (NM_004992.3) is 0.058% in European (non-Finnish) sub population and 0.033% in 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). In summary, the c.-187_-186del variant in MECP2 is classified as benign based on the ACMG/AMP criteria (BA1).
GeneDx RCV000144799 SCV000191024 likely benign not specified 2017-11-02 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000144799 SCV001362256 benign not specified 2019-05-17 criteria provided, single submitter clinical testing Variant summary: MECP2 c.-187_-186delAG is located in the untranslated mRNA region upstream of the initiation codon. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00025 in 44218 control chromosomes (gnomAD). The observed variant frequency is approximately 30 fold of the estimated maximal expected allele frequency for a pathogenic variant in MECP2 causing Rett Syndrome phenotype (8.3e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.-187_-186delAG in individuals affected with Rett Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV001522613 SCV001732188 benign Severe neonatal-onset encephalopathy with microcephaly 2020-09-10 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000144799 SCV002066933 likely benign not specified 2017-11-08 criteria provided, single submitter clinical testing
RettBASE RCV000170283 SCV000222615 uncertain significance X-linked intellectual disability-psychosis-macroorchidism syndrome 2007-11-01 no assertion criteria provided curation

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