NM_001110792.2(MECP2):c.1444_1447delinsTG (p.Asn482fs) AND Rett syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 14, 2023
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:: RCV000170159.2

Allele description [Variation Report for NM_001110792.2(MECP2):c.1444_1447delinsTG (p.Asn482fs)]

NM_001110792.2(MECP2):c.1444_1447delinsTG (p.Asn482fs)

Gene:

MECP2:methyl-CpG binding protein 2 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_001110792.2(MECP2):c.1444_1447delinsTG (p.Asn482fs)

Other names:

NM_001110792.2(MECP2):c.1444_1447delinsTG; p.Asn482fs

HGVS:

NC_000023.11:g.154030417_154030420delinsCA
NG_007107.3:g.111684_111687delinsTG
NM_001110792.2:c.1444_1447delinsTGMANE SELECT
NM_001316337.2:c.1129_1132delinsTG
NM_001369391.2:c.1129_1132delinsTG
NM_001369392.2:c.1129_1132delinsTG
NM_001369393.2:c.1129_1132delinsTG
NM_001369394.2:c.1129_1132delinsTG
NM_001386137.1:c.739_742delinsTG
NM_001386138.1:c.739_742delinsTG
NM_001386139.1:c.739_742delinsTG
NM_004992.4:c.1408_1411delinsTG
NP_001104262.1:p.Asn482fs
NP_001303266.1:p.Asn377fs
NP_001356320.1:p.Asn377fs
NP_001356321.1:p.Asn377fs
NP_001356322.1:p.Asn377fs
NP_001356323.1:p.Asn377fs
NP_001373066.1:p.Asn247fs
NP_001373067.1:p.Asn247fs
NP_001373068.1:p.Asn247fs
NP_004983.1:p.Asn470fs
LRG_764t1:c.1444_1447delinsTG
LRG_764t2:c.1408_1411delinsTG
LRG_764:g.111684_111687delinsTG
LRG_764p1:p.Asn482fs
LRG_764p2:p.Asn470fs
NC_000023.10:g.153295868_153295871delinsCA
NG_007107.2:g.111708_111711delinsTG

Protein change:

N247fs

Links:

dbSNP: rs786205023

NCBI 1000 Genomes Browser:

rs786205023

Molecular consequence:

NM_001110792.2:c.1444_1447delinsTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001316337.2:c.1129_1132delinsTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369391.2:c.1129_1132delinsTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369392.2:c.1129_1132delinsTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369393.2:c.1129_1132delinsTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001369394.2:c.1129_1132delinsTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386137.1:c.739_742delinsTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386138.1:c.739_742delinsTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001386139.1:c.739_742delinsTG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004992.4:c.1408_1411delinsTG - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

Clear Turn Off Turn On

hypothetical protein Z578_00282 [Mycobacterium tuberculosis 1430BH]
hypothetical protein Z578_00282 [Mycobacterium tuberculosis 1430BH]
gi|621168093|gb|KAN70554.1||gnl|WGS |Z578_00282T0

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000222488	RettBASE	no assertion criteria provided	Pathogenic (Feb 5, 2014)	unknown	curation	PubMed (1) [See all records that cite this PMID]
SCV004098811	Centre for Population Genomics, CPG	criteria provided, single submitter (McKnight et al. (Hum Mutat. 2022))	Uncertain significance (Aug 14, 2023)	germline	curation	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

SCV000222488

RettBASE

no assertion criteria provided

Pathogenic
(Feb 5, 2014)

unknown

curation

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

SCV004098811

Centre for Population Genomics, CPG

criteria provided, single submitter

(McKnight et al. (Hum Mutat. 2022))

Uncertain significance
(Aug 14, 2023)

germline

curation

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	unknown	yes	1	not provided	not provided	1	No	curation

Citations

PubMed

Detection of rarely identified multiple mutations in MECP2 gene do not contribute to enhanced severity in Rett syndrome.

Chapleau CA, Lane J, Kirwin SM, Schanen C, Vinette KM, Stubbolo D, MacLeod P, Glaze DG, Motil KJ, Neul JL, Skinner SA, Kaufmann WE, Percy AK.

Am J Med Genet A. 2013 Jul;161A(7):1638-46. doi: 10.1002/ajmg.a.35979. Epub 2013 May 21. Erratum in: Am J Med Genet A. 2014 May;164A(5):1346. Glaze, Daniel G [added]; Motil, Kathleen J [added]; Neul, Jeffrey L [added]; Skinner, Steven A [added]; Kaufmann, Walter E [added].

PubMed [citation]

PMID:: 23696494
PMCID:: PMC3689857

Recommendations by the ClinGen Rett/Angelman-like expert panel for gene-specific variant interpretation methods.

McKnight D, Bean L, Karbassi I, Beattie K, Bienvenu T, Bonin H, Fang P, Chrisodoulou J, Friez M, Helgeson M, Krishnaraj R, Meng L, Mighion L, Neul J, Percy A, Ramsden S, Zoghbi H, Das S.

Hum Mutat. 2022 Aug;43(8):1097-1113. doi: 10.1002/humu.24302. Epub 2021 Dec 2.

PubMed [citation]

PMID:: 34837432
PMCID:: PMC9135956

Details of each submission

From RettBASE, SCV000222488.1

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

Description

"Rett syndrome - not certain"

PubMed [ID: 23696494]

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

From Centre for Population Genomics, CPG, SCV004098811.1

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

Description

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 a variant of uncertain significance. At least the following criteria are met: Protein length changes due to stop-loss variant (PM4_Strong). This variant is absent from gnomAD (PM2_Supporting).

#	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: Oct 28, 2023

ClinVar

Relating variation to medicine