rs786205018
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM1BP4_ModerateBS2_Supporting
The NM_001110792.2(MECP2):c.868G>A(p.Ala290Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 1,098,187 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A290V) has been classified as Likely benign.
Frequency
Consequence
NM_001110792.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.868G>A | p.Ala290Thr | missense_variant | 3/3 | ENST00000453960.7 | |
MECP2 | NM_004992.4 | c.832G>A | p.Ala278Thr | missense_variant | 4/4 | ENST00000303391.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000453960.7 | c.868G>A | p.Ala290Thr | missense_variant | 3/3 | 1 | NM_001110792.2 | ||
MECP2 | ENST00000303391.11 | c.832G>A | p.Ala278Thr | missense_variant | 4/4 | 1 | NM_004992.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 exomes AF: 0.0000275 AC: 5AN: 182147Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67441
GnomAD4 exome AF: 0.00000911 AC: 10AN: 1098187Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 2AN XY: 363561
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Rett syndrome Benign:2
Likely benign, criteria provided, single submitter | curation | Centre for Population Genomics, CPG | Aug 14, 2023 | 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 2.0, this variant is classified as likely 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 1 individual with no features of Rett Syndrome (BS2_Supporting, PMID 23696494). The variant has been observed in trans with a MECP2 pathogenic variant (BP2, PMID 23696494) - |
Likely benign, criteria provided, single submitter | clinical testing | Molecular Diagnostics Lab, Nemours Children's Health, Delaware | Jul 09, 2015 | - - |
Severe neonatal-onset encephalopathy with microcephaly Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 19, 2023 | - - |
not specified Benign:1
Benign, no assertion criteria provided | curation | RettBASE | Feb 05, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at