rs1557134481
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001110792.2(MECP2):c.1182_*452del variant causes a stop lost, 3 prime UTR change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Consequence
MECP2
NM_001110792.2 stop_lost, 3_prime_UTR
NM_001110792.2 stop_lost, 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.71
Genes affected
MECP2 (HGNC:6990): (methyl-CpG binding protein 2) DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. In contrast to other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 is dispensible in stem cells, but is essential for embryonic development. MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common causes of cognitive disability in females. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Stoplost variant. No alternative stopcodon identified downstream, so we assume a Nonstop Mediated Decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-154029914-GAGTGGGGGAGGTGGGGGGAGCTGGGGGAGCTGTAGACGGGGCACTGATGGCACCGAAAACGGGAGTGTCCTCTCAACTGCTCTGTCGCTCTGTCTCTAACGACCACATGGGGGAAAGGTTTGGGCGGGAGGGGAGGTGCCTGGTCAACAGCTTGTCTGGTCAGTAGTATCTGCAGCAAGCCTTGTTGAAGGAGCCTAGTTTAGAAAAGTGCAAAGCTACTTCTGGCCCTGGTTAGGTCTTCAACCTGACTGTGCTTGTCGGTAAGAAAAACATCCCCAATGCTCCAACTACTCCCACCCTGAAGCCACGAAACTCTAAGTTTACTGAAAGAAAAAAAAATATTTTTTATTTCAGTTAATCGGGAAGCTTTGTCAGAGCCCTACCCATAAGGAGAAGAGACAACAGCTGCCTTTATTCTTGTTGGTTTGCTTTGCAATCCGCTCCGTGTAAAGTCAGCTAACTCTCTCGGTCACGGGCGTCCGGCTGTCCACAGGCTCCTCTCTGTTTGGCCTTGGCATGGAGGATGAAACAATGTCTTTGCGCTCTCCCTCCCCTCGGTGTTTGTACTTTTCTGCGGCCGTGGCGGCGGTGGCAACCGCGGGCTGAGTCTTAGCTGGCTCCTTGGGGCAGCCGTCGCTCTCCAGTGAGCCTCCTCTGGGCATCTTCTCCTCTTTGCAGACGCTGCTGCTCAAGTCCTGGGGCTCAGGGGGGCTGGTGGGGTCCTCGGAGCTCTCGGGCTCAGGTGGAGGTGGGGGCAGGGGTGGGAGC-G is Pathogenic according to our data. Variant chrX-154029914-GAGTGGGGGAGGTGGGGGGAGCTGGGGGAGCTGTAGACGGGGCACTGATGGCACCGAAAACGGGAGTGTCCTCTCAACTGCTCTGTCGCTCTGTCTCTAACGACCACATGGGGGAAAGGTTTGGGCGGGAGGGGAGGTGCCTGGTCAACAGCTTGTCTGGTCAGTAGTATCTGCAGCAAGCCTTGTTGAAGGAGCCTAGTTTAGAAAAGTGCAAAGCTACTTCTGGCCCTGGTTAGGTCTTCAACCTGACTGTGCTTGTCGGTAAGAAAAACATCCCCAATGCTCCAACTACTCCCACCCTGAAGCCACGAAACTCTAAGTTTACTGAAAGAAAAAAAAATATTTTTTATTTCAGTTAATCGGGAAGCTTTGTCAGAGCCCTACCCATAAGGAGAAGAGACAACAGCTGCCTTTATTCTTGTTGGTTTGCTTTGCAATCCGCTCCGTGTAAAGTCAGCTAACTCTCTCGGTCACGGGCGTCCGGCTGTCCACAGGCTCCTCTCTGTTTGGCCTTGGCATGGAGGATGAAACAATGTCTTTGCGCTCTCCCTCCCCTCGGTGTTTGTACTTTTCTGCGGCCGTGGCGGCGGTGGCAACCGCGGGCTGAGTCTTAGCTGGCTCCTTGGGGCAGCCGTCGCTCTCCAGTGAGCCTCCTCTGGGCATCTTCTCCTCTTTGCAGACGCTGCTGCTCAAGTCCTGGGGCTCAGGGGGGCTGGTGGGGTCCTCGGAGCTCTCGGGCTCAGGTGGAGGTGGGGGCAGGGGTGGGAGC-G is described in ClinVar as [Pathogenic]. Clinvar id is 192292.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.1182_*452del | stop_lost, 3_prime_UTR_variant | 3/3 | ENST00000453960.7 | ||
MECP2 | NM_004992.4 | c.1146_*452del | stop_lost, 3_prime_UTR_variant | 4/4 | ENST00000303391.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000303391.11 | c.1146_*452del | stop_lost, 3_prime_UTR_variant | 4/4 | 1 | NM_004992.4 | P1 | ||
MECP2 | ENST00000453960.7 | c.1182_*452del | stop_lost, 3_prime_UTR_variant | 3/3 | 1 | NM_001110792.2 | |||
MECP2 | ENST00000407218.5 | 3_prime_UTR_variant | 4/4 | 5 | |||||
MECP2 | ENST00000628176.2 | 3_prime_UTR_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rett syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, Children's Mercy Hospital and Clinics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at