NM_001110792.2(MECP2):c.789C>T (p.Pro263=) AND not specified

Clinical significance:Benign/Likely benign (Last evaluated: Feb 15, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000133227.7

Allele description [Variation Report for NM_001110792.2(MECP2):c.789C>T (p.Pro263=)]

NM_001110792.2(MECP2):c.789C>T (p.Pro263=)

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.789C>T (p.Pro263=)
HGVS:
  • NC_000023.11:g.154031075G>A
  • NG_007107.2:g.111053C>T
  • NG_007107.3:g.111029C>T
  • NM_001110792.2:c.789C>TMANE SELECT
  • NM_001316337.2:c.474C>T
  • NM_001369391.2:c.474C>T
  • NM_001369392.2:c.474C>T
  • NM_001369393.2:c.474C>T
  • NM_001369394.2:c.474C>T
  • NM_001386137.1:c.84C>T
  • NM_001386138.1:c.84C>T
  • NM_001386139.1:c.84C>T
  • NM_004992.3:c.753C>T
  • NM_004992.4:c.753C>T
  • NP_001104262.1:p.Pro263=
  • NP_001303266.1:p.Pro158=
  • NP_001356320.1:p.Pro158=
  • NP_001356321.1:p.Pro158=
  • NP_001356322.1:p.Pro158=
  • NP_001356323.1:p.Pro158=
  • NP_001373066.1:p.Pro28=
  • NP_001373067.1:p.Pro28=
  • NP_001373068.1:p.Pro28=
  • NP_004983.1:p.Pro251=
  • NP_004983.1:p.Pro251=
  • LRG_764t1:c.789C>T
  • LRG_764t2:c.753C>T
  • AJ132917.1:c.753C>T
  • LRG_764:g.111029C>T
  • LRG_764p1:p.Pro263=
  • LRG_764p2:p.Pro251=
  • NC_000023.10:g.153296526G>A
Links:
dbSNP: rs63582063
NCBI 1000 Genomes Browser:
rs63582063
Molecular consequence:
  • NM_001110792.2:c.789C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001316337.2:c.474C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001369391.2:c.474C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001369392.2:c.474C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001369393.2:c.474C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001369394.2:c.474C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001386137.1:c.84C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001386138.1:c.84C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001386139.1:c.84C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_004992.3:c.753C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_004992.4:c.753C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000188227RettBASEno assertion criteria providedBenign
(Nov 1, 2011)
unknowncuration

PubMed (2)
[See all records that cite these PMIDs]

SCV000193640Genetic Services Laboratory,University of Chicagocriteria provided, single submitter
Likely benign
(Apr 10, 2015)
germlineclinical testing

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

SCV000310762PreventionGenetics,PreventionGeneticscriteria provided, single submitter
Likely benigngermlineclinical testing

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

SCV001362254Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Benign
(Feb 15, 2019)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownnot provided3not providednot provided3Nocuration

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

Comprehensive diagnosis of Rett's syndrome relying on genetic, epigenetic and expression evidence of deficiency of the methyl-CpG-binding protein 2 gene: study of a cohort of Israeli patients.

Petel-Galil Y, Benteer B, Galil YP, Zeev BB, Greenbaum I, Vecsler M, Goldman B, Lohi H, Minassian BA, Gak E.

J Med Genet. 2006 Dec;43(12):e56.

PubMed [citation]
PMID:
17142618
PMCID:
PMC2563193
See all PubMed Citations (5)

Details of each submission

From RettBASE, SCV000188227.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providedNocuration PubMed (2)
2not provided1not providedNocuration PubMed (2)
3not provided1not providedNocuration PubMed (2)

Description

"Rett syndrome - not certain"
"Rett syndrome - classical"
"Rett syndrome - not certain"
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownnot provided1bloodnot provided1not providednot providednot provided
2unknownnot provided1bloodnot provided1not providednot providednot provided
3unknownnot provided1bloodnot provided1not providednot providednot provided

From Genetic Services Laboratory,University of Chicago, SCV000193640.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From PreventionGenetics,PreventionGenetics, SCV000310762.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362254.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: The variant, MECP2 c.753C>T results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00015 in 199952 control chromosomes (14 hemizygotes), predominantly at a frequency of 0.00051 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 61-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in MECP2 causing Rett Syndrome phenotype (8.3e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. The variant, c.753C>T has been reported in the literature in individuals affected with Rett Syndrome (Chae_2004, Petel-Galil_2006, Temudo_2009, Hadzsiev_2011). However, these reports do not provide unequivocal conclusions about association of the variant with Rett Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.

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

Last Updated: Nov 27, 2021

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