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NM_001110792.2(MECP2):c.289C>T (p.Arg97Cys) AND Rett syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Dec 8, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV001775123.2

Allele description [Variation Report for NM_001110792.2(MECP2):c.289C>T (p.Arg97Cys)]

NM_001110792.2(MECP2):c.289C>T (p.Arg97Cys)

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.289C>T (p.Arg97Cys)
Other names:
NM_001110792.2(MECP2):c.289C>T; p.Arg97Cys
HGVS:
  • NC_000023.11:g.154032331G>A
  • NG_007107.3:g.109773C>T
  • NM_001110792.2:c.289C>TMANE SELECT
  • NM_001316337.2:c.-27C>T
  • NM_001369391.2:c.-27C>T
  • NM_001369392.2:c.-27C>T
  • NM_001369393.2:c.-27C>T
  • NM_001369394.2:c.-27C>T
  • NM_001386137.1:c.-308C>T
  • NM_001386138.1:c.-308C>T
  • NM_001386139.1:c.-308C>T
  • NM_004992.4:c.253C>T
  • NP_001104262.1:p.Arg97Cys
  • NP_004983.1:p.Arg85Cys
  • NP_004983.1:p.Arg85Cys
  • LRG_764t1:c.289C>T
  • LRG_764t2:c.253C>T
  • LRG_764:g.109773C>T
  • LRG_764p1:p.Arg97Cys
  • LRG_764p2:p.Arg85Cys
  • NC_000023.10:g.153297782G>A
  • NC_000023.10:g.153297782G>A
  • NG_007107.2:g.109797C>T
  • NM_004992.3:c.253C>T
Protein change:
R85C
Links:
dbSNP: rs1064797047
NCBI 1000 Genomes Browser:
rs1064797047
Molecular consequence:
  • NM_001316337.2:c.-27C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001369391.2:c.-27C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001369392.2:c.-27C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001369393.2:c.-27C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001369394.2:c.-27C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001386137.1:c.-308C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001386138.1:c.-308C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001386139.1:c.-308C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001110792.2:c.289C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004992.4:c.253C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Rett syndrome (RTT)
Synonyms:
Autism, dementia, ataxia, and loss of purposeful hand use; Rett's disorder
Identifiers:
MONDO: MONDO:0010726; MedGen: C0035372; Orphanet: 3095; Orphanet: 778; OMIM: 312750

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV0020121173billion
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Oct 2, 2021) 		germlineclinical testing

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

SCV002769729ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel
reviewed by expert panel

(ClinGen RettAS ACMG Specifications V2)		Uncertain significance
(Dec 8, 2022) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From 3billion, SCV002012117.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with supporting evidence (ClinVar ID: VCV000985267.2, PS1_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.00000546, PM2). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.843, 3Cnet: 0.995, PP3). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

From ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel, SCV002769729.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The p.Arg85Cys variant in MECP2 (NM_004992.3) occurs in the de novo state (biological parentage unconfirmed) in one individual (3billion) (PM6). The p.Arg85Cys variant in MECP2 (NM_004992.3) is found in a patient with an alternate molecular basis of disease (internal database) (BP5). The p.Arg85Cys variant in MECP2 (NM_004992.3) is observed in 1 unaffected individuals (internal database) (BS2_supporting). Computational prediction analysis tools are inconclusive for this variant. In summary, the p.Arg85Cys variant in MECP2 (NM_004992.3) is classified as a variant of unknown significance based on the ACMG/AMP criteria (PM6, BP5, BS2_supporting).

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

Last Updated: Feb 28, 2024