NM_002397.5(MEF2C):c.881del (p.Pro294fs) AND Intellectual disability, autosomal dominant 20

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 2, 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:: RCV003015781.3

Allele description [Variation Report for NM_002397.5(MEF2C):c.881del (p.Pro294fs)]

NM_002397.5(MEF2C):c.881del (p.Pro294fs)

Gene:

MEF2C:myocyte enhancer factor 2C [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q14.3

Genomic location:

Preferred name:

NM_002397.5(MEF2C):c.881del (p.Pro294fs)

HGVS:

NC_000005.10:g.88729304del
NG_023427.1:g.179805del
NM_001131005.2:c.851del
NM_001193347.1:c.911del
NM_001193348.1:c.713del
NM_001193349.3:c.737del
NM_001193350.2:c.881del
NM_001308002.3:c.857del
NM_001363581.2:c.881del
NM_001364329.2:c.881del
NM_001364330.2:c.881del
NM_001364331.2:c.881del
NM_001364332.2:c.737del
NM_001364333.2:c.857del
NM_001364334.2:c.881del
NM_001364335.2:c.881del
NM_001364336.2:c.881del
NM_001364337.2:c.881del
NM_001364338.2:c.911del
NM_001364339.2:c.857del
NM_001364340.2:c.857del
NM_001364341.2:c.857del
NM_001364342.2:c.857del
NM_001364343.2:c.851del
NM_001364344.2:c.737del
NM_001364345.2:c.881del
NM_001364346.2:c.881del
NM_001364347.2:c.881del
NM_001364348.2:c.857del
NM_001364349.2:c.857del
NM_001364350.2:c.857del
NM_001364352.2:c.851del
NM_001364353.2:c.503del
NM_001364354.2:c.737del
NM_001364355.2:c.737del
NM_001364356.2:c.503del
NM_001364357.2:c.431del
NM_002397.5:c.881delMANE SELECT
NP_001124477.1:p.Pro284fs
NP_001180276.1:p.Pro304fs
NP_001180277.1:p.Pro238fs
NP_001180278.1:p.Pro246fs
NP_001180279.1:p.Pro294fs
NP_001294931.1:p.Pro286fs
NP_001350510.1:p.Pro294fs
NP_001351258.1:p.Pro294fs
NP_001351259.1:p.Pro294fs
NP_001351260.1:p.Pro294fs
NP_001351261.1:p.Pro246fs
NP_001351262.1:p.Pro286fs
NP_001351263.1:p.Pro294fs
NP_001351264.1:p.Pro294fs
NP_001351265.1:p.Pro294fs
NP_001351266.1:p.Pro294fs
NP_001351267.1:p.Pro304fs
NP_001351268.1:p.Pro286fs
NP_001351269.1:p.Pro286fs
NP_001351270.1:p.Pro286fs
NP_001351271.1:p.Pro286fs
NP_001351272.1:p.Pro284fs
NP_001351273.1:p.Pro246fs
NP_001351274.1:p.Pro294fs
NP_001351275.1:p.Pro294fs
NP_001351276.1:p.Pro294fs
NP_001351277.1:p.Pro286fs
NP_001351278.1:p.Pro286fs
NP_001351279.1:p.Pro286fs
NP_001351281.1:p.Pro284fs
NP_001351282.1:p.Pro168fs
NP_001351283.1:p.Pro246fs
NP_001351284.1:p.Pro246fs
NP_001351285.1:p.Pro168fs
NP_001351286.1:p.Pro144fs
NP_002388.2:p.Pro294fs
NC_000005.9:g.88025118del
NC_000005.9:g.88025121del

Protein change:

P144fs

Molecular consequence:

NM_001131005.2:c.851del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001193347.1:c.911del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001193348.1:c.713del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001193349.3:c.737del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001193350.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001308002.3:c.857del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363581.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364329.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364330.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364331.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364332.2:c.737del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364333.2:c.857del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364334.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364335.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364336.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364337.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364338.2:c.911del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364339.2:c.857del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364340.2:c.857del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364341.2:c.857del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364342.2:c.857del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364343.2:c.851del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364344.2:c.737del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364345.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364346.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364347.2:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364348.2:c.857del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364349.2:c.857del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364350.2:c.857del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364352.2:c.851del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364353.2:c.503del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364354.2:c.737del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364355.2:c.737del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364356.2:c.503del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001364357.2:c.431del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002397.5:c.881del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Intellectual disability, autosomal dominant 20 (NEDHSIL)
Synonyms:: NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, STEREOTYPIC HAND MOVEMENTS, AND IMPAIRED LANGUAGE
Identifiers:: MONDO: MONDO:0013266; MedGen: C3150700; Orphanet: 228384; OMIM: 613443

Recent activity

Clear Turn Off Turn On

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
SCV003308232	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 2, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20513142, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003308232

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 2, 2022)

germline

clinical testing

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

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	clinical testing

Citations

PubMed

Mutations in MEF2C from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 expression.

Zweier M, Gregor A, Zweier C, Engels H, Sticht H, Wohlleber E, Bijlsma EK, Holder SE, Zenker M, Rossier E, Grasshoff U, Johnson DS, Robertson L, Firth HV; Cornelia Kraus., Ekici AB, Reis A, Rauch A.

Hum Mutat. 2010 Jun;31(6):722-33. doi: 10.1002/humu.21253.

PubMed [citation]

PMID:: 20513142

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003308232.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Pro294Glnfs*5) in the MEF2C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MEF2C are known to be pathogenic (PMID: 20513142). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MEF2C-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine