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NM_001110792.2(MECP2):c.286C>T (p.Arg96Trp) AND Severe neonatal-onset encephalopathy with microcephaly

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 27, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000645117.7

Allele description

NM_001110792.2(MECP2):c.286C>T (p.Arg96Trp)

Gene:
MECP2:methyl-CpG binding protein 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_001110792.2(MECP2):c.286C>T (p.Arg96Trp)
HGVS:
  • NC_000023.11:g.154032334G>A
  • NG_007107.3:g.109770C>T
  • NM_001110792.2:c.286C>TMANE SELECT
  • NM_001316337.2:c.-30C>T
  • NM_001369391.2:c.-30C>T
  • NM_001369392.2:c.-30C>T
  • NM_001369393.2:c.-30C>T
  • NM_001369394.2:c.-30C>T
  • NM_001386137.1:c.-311C>T
  • NM_001386138.1:c.-311C>T
  • NM_001386139.1:c.-311C>T
  • NM_004992.4:c.250C>T
  • NP_001104262.1:p.Arg96Trp
  • NP_004983.1:p.Arg84Trp
  • NP_004983.1:p.Arg84Trp
  • LRG_764t1:c.286C>T
  • LRG_764t2:c.250C>T
  • LRG_764:g.109770C>T
  • LRG_764p1:p.Arg96Trp
  • LRG_764p2:p.Arg84Trp
  • NC_000023.10:g.153297785G>A
  • NG_007107.2:g.109794C>T
  • NM_004992.3:c.250C>T
Protein change:
R84W
Links:
dbSNP: rs1557137821
NCBI 1000 Genomes Browser:
rs1557137821
Molecular consequence:
  • NM_001316337.2:c.-30C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001369391.2:c.-30C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001369392.2:c.-30C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001369393.2:c.-30C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001369394.2:c.-30C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001386137.1:c.-311C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001386138.1:c.-311C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001386139.1:c.-311C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001110792.2:c.286C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004992.4:c.250C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Severe neonatal-onset encephalopathy with microcephaly
Synonyms:
Encephalopathy, neonatal severe; Encephalopathy, neonatal severe, due to MECP2 mutations
Identifiers:
MONDO: MONDO:0010397; MedGen: C1968556; Orphanet: 209370; OMIM: 300673

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000766859Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 27, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000766859.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 84 of the MECP2 protein (p.Arg84Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MECP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 536586). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MECP2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 7, 2023