NM_001110792.2(MECP2):c.669G>C (p.Arg223Ser) AND not specified

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Apr 10, 2019
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:: RCV000133184.7

Allele description [Variation Report for NM_001110792.2(MECP2):c.669G>C (p.Arg223Ser)]

NM_001110792.2(MECP2):c.669G>C (p.Arg223Ser)

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.669G>C (p.Arg223Ser)

Other names:

NM_001110792.2(MECP2):c.669G>C; p.Arg223Ser

HGVS:

NC_000023.11:g.154031195C>G
NG_007107.3:g.110909G>C
NM_001110792.2:c.669G>CMANE SELECT
NM_001316337.2:c.354G>C
NM_001369391.2:c.354G>C
NM_001369392.2:c.354G>C
NM_001369393.2:c.354G>C
NM_001369394.2:c.354G>C
NM_001386137.1:c.-37G>C
NM_001386138.1:c.-37G>C
NM_001386139.1:c.-37G>C
NM_004992.4:c.633G>C
NP_001104262.1:p.Arg223Ser
NP_001303266.1:p.Arg118Ser
NP_001356320.1:p.Arg118Ser
NP_001356321.1:p.Arg118Ser
NP_001356322.1:p.Arg118Ser
NP_001356323.1:p.Arg118Ser
NP_004983.1:p.Arg211Ser
NP_004983.1:p.Arg211Ser
LRG_764t1:c.669G>C
LRG_764t2:c.633G>C
AJ132917.1:c.633G>C
LRG_764:g.110909G>C
LRG_764p1:p.Arg223Ser
LRG_764p2:p.Arg211Ser
NC_000023.10:g.153296646C>G
NG_007107.2:g.110933G>C
NM_004992.3:c.633G>C

Protein change:

R118S

Links:

dbSNP: rs61749731

NCBI 1000 Genomes Browser:

rs61749731

Molecular consequence:

NM_001386137.1:c.-37G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386138.1:c.-37G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001386139.1:c.-37G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001110792.2:c.669G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001316337.2:c.354G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369391.2:c.354G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369392.2:c.354G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369393.2:c.354G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369394.2:c.354G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004992.4:c.633G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000188182	RettBASE	no assertion criteria provided	Benign (Dec 5, 2013)	paternal, unknown	curation	PubMed (1) [See all records that cite this PMID]
SCV001362251	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Apr 10, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000188182

RettBASE

no assertion criteria provided

Benign
(Dec 5, 2013)

paternal, unknown

curation

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

SCV001362251

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely benign
(Apr 10, 2019)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	paternal	not provided	1	not provided	not provided	1	not provided	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	not provided	2	not provided	not provided	2	No	curation

Citations

PubMed

MECP2 gene study in a large cohort: testing of 240 female patients and 861 healthy controls (519 females and 342 males).

Maortua H, Martínez-Bouzas C, García-Ribes A, Martínez MJ, Guillen E, Domingo MR, Calvo MT, Guitart M, Gabau E, Botella MP, Gener B, Rubio I, López-Aríztegui MA, Tejada MI.

J Mol Diagn. 2013 Sep;15(5):723-9. doi: 10.1016/j.jmoldx.2013.05.002. Epub 2013 Jun 26.

PubMed [citation]

PMID:: 23810759

Details of each submission

From RettBASE, SCV000188182.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	No	curation	PubMed (1)
2	not provided	1	not provided	not provided	curation	PubMed (1)
3	not provided	1	not provided	not provided	curation	PubMed (1)

Description

Not Rett synd. - normal control

Rett syndrome - Classical

"Not Rett synd. - Unaffected family member"

PubMed [ID: 23810759]

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	not provided	1	not stated	not provided		1	not provided	not provided	not provided
2	paternal	not provided	1	Blood or skin	not provided		1	not provided	not provided	not provided
3	unknown	not provided	1	Blood or skin	not provided		1	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362251.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: MECP2 c.633G>C (p.Arg211Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0002 in 199776 control chromosomes (gnomAD). The observed variant frequency is approximately 24 fold of 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 benign. To our knowledge, no occurrence of c.633G>C in individuals affected with Rett Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (1x likely benign, 1x benign). Based on the evidence outlined above, the variant was classified as likely benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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