rs267608392
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4
The NM_001110792.2(MECP2):c.1188_1208delACCCCTGCCCCCACCTCCACC(p.Pro397_Pro403del) variant causes a disruptive inframe deletion change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000022 ( 0 hom., 0 hem., cov: 0)
Exomes 𝑓: 0.0000013 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
MECP2
NM_001110792.2 disruptive_inframe_deletion
NM_001110792.2 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.01
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 Uncertain_significance. Variant got 2 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_001110792.2.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.1188_1208delACCCCTGCCCCCACCTCCACC | p.Pro397_Pro403del | disruptive_inframe_deletion | 3/3 | ENST00000453960.7 | NP_001104262.1 | |
MECP2 | NM_004992.4 | c.1152_1172delACCCCTGCCCCCACCTCCACC | p.Pro385_Pro391del | disruptive_inframe_deletion | 4/4 | ENST00000303391.11 | NP_004983.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000453960.7 | c.1188_1208delACCCCTGCCCCCACCTCCACC | p.Pro397_Pro403del | disruptive_inframe_deletion | 3/3 | 1 | NM_001110792.2 | ENSP00000395535.2 | ||
MECP2 | ENST00000303391.11 | c.1152_1172delACCCCTGCCCCCACCTCCACC | p.Pro385_Pro391del | disruptive_inframe_deletion | 4/4 | 1 | NM_004992.4 | ENSP00000301948.6 | ||
MECP2 | ENST00000407218 | c.*524_*544delACCCCTGCCCCCACCTCCACC | 3_prime_UTR_variant | 4/4 | 5 | ENSP00000384865.2 | ||||
MECP2 | ENST00000628176 | c.*524_*544delACCCCTGCCCCCACCTCCACC | 3_prime_UTR_variant | 5/5 | 3 | ENSP00000486978.1 |
Frequencies
GnomAD3 genomes AF: 0.0000220 AC: 1AN: 45532Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 10470
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000134 AC: 1AN: 748978Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 224762
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GnomAD4 genome AF: 0.0000220 AC: 1AN: 45532Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 10470
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at