rs372500343
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP7BA1BP4
This summary comes from the ClinGen Evidence Repository: 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). LINK:https://erepo.genome.network/evrepo/ui/classification/CA243345/MONDO:0010726/032
Frequency
Consequence
NM_001316337.2 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.90C>G | p.Leu30Leu | synonymous_variant | 2/3 | ENST00000453960.7 | NP_001104262.1 | |
MECP2 | NM_004992.4 | c.54C>G | p.Leu18Leu | synonymous_variant | 3/4 | ENST00000303391.11 | NP_004983.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000622 AC: 7AN: 112613Hom.: 0 Cov.: 24 AF XY: 0.0000288 AC XY: 1AN XY: 34747
GnomAD3 exomes AF: 0.0000336 AC: 6AN: 178410Hom.: 0 AF XY: 0.0000152 AC XY: 1AN XY: 65586
GnomAD4 exome AF: 0.00000366 AC: 4AN: 1094125Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 1AN XY: 361283
GnomAD4 genome AF: 0.0000621 AC: 7AN: 112667Hom.: 0 Cov.: 24 AF XY: 0.0000287 AC XY: 1AN XY: 34811
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 27, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 23, 2020 | - - |
Severe neonatal-onset encephalopathy with microcephaly Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 29, 2024 | - - |
Rett syndrome Benign:1
Benign, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Jun 15, 2023 | 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). - |
MECP2-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 24, 2023 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at