NM_002397.5(MEF2C):c.258G>A (p.Glu86=) AND Intellectual disability, autosomal dominant 20

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 19, 2020
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:: RCV002472269.1

Allele description [Variation Report for NM_002397.5(MEF2C):c.258G>A (p.Glu86=)]

NM_002397.5(MEF2C):c.258G>A (p.Glu86=)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

5q14.3

Genomic location:

Preferred name:

NM_002397.5(MEF2C):c.258G>A (p.Glu86=)

HGVS:

NC_000005.10:g.88804598C>T
NG_023427.1:g.104508G>A
NM_001131005.2:c.258G>A
NM_001193347.1:c.258G>A
NM_001193348.1:c.258G>A
NM_001193349.3:c.258G>A
NM_001193350.2:c.258G>A
NM_001308002.3:c.258G>A
NM_001363581.2:c.258G>A
NM_001364329.2:c.258G>A
NM_001364330.2:c.258G>A
NM_001364331.2:c.258G>A
NM_001364332.2:c.258G>A
NM_001364333.2:c.258G>A
NM_001364334.2:c.258G>A
NM_001364335.2:c.258G>A
NM_001364336.2:c.258G>A
NM_001364337.2:c.258G>A
NM_001364338.2:c.258G>A
NM_001364339.2:c.258G>A
NM_001364340.2:c.258G>A
NM_001364341.2:c.258G>A
NM_001364342.2:c.258G>A
NM_001364343.2:c.258G>A
NM_001364344.2:c.258G>A
NM_001364345.2:c.258G>A
NM_001364346.2:c.258G>A
NM_001364347.2:c.258G>A
NM_001364348.2:c.258G>A
NM_001364349.2:c.258G>A
NM_001364350.2:c.258G>A
NM_001364352.2:c.258G>A
NM_001364354.2:c.258G>A
NM_001364355.2:c.258G>A
NM_002397.5:c.258G>AMANE SELECT
NP_001124477.1:p.Glu86=
NP_001180276.1:p.Glu86=
NP_001180277.1:p.Glu86=
NP_001180278.1:p.Glu86=
NP_001180279.1:p.Glu86=
NP_001294931.1:p.Glu86=
NP_001350510.1:p.Glu86=
NP_001351258.1:p.Glu86=
NP_001351259.1:p.Glu86=
NP_001351260.1:p.Glu86=
NP_001351261.1:p.Glu86=
NP_001351262.1:p.Glu86=
NP_001351263.1:p.Glu86=
NP_001351264.1:p.Glu86=
NP_001351265.1:p.Glu86=
NP_001351266.1:p.Glu86=
NP_001351267.1:p.Glu86=
NP_001351268.1:p.Glu86=
NP_001351269.1:p.Glu86=
NP_001351270.1:p.Glu86=
NP_001351271.1:p.Glu86=
NP_001351272.1:p.Glu86=
NP_001351273.1:p.Glu86=
NP_001351274.1:p.Glu86=
NP_001351275.1:p.Glu86=
NP_001351276.1:p.Glu86=
NP_001351277.1:p.Glu86=
NP_001351278.1:p.Glu86=
NP_001351279.1:p.Glu86=
NP_001351281.1:p.Glu86=
NP_001351283.1:p.Glu86=
NP_001351284.1:p.Glu86=
NP_002388.2:p.Glu86=
NC_000005.9:g.88100415C>T
NM_002397.4:c.258G>A

Links:

dbSNP: rs796052724

NCBI 1000 Genomes Browser:

rs796052724

Molecular consequence:

NM_001131005.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001193347.1:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001193348.1:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001193349.3:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001193350.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001308002.3:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001363581.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364329.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364330.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364331.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364332.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364333.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364334.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364335.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364336.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364337.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364338.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364339.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364340.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364341.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364342.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364343.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364344.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364345.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364346.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364347.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364348.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364349.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364350.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364352.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364354.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001364355.2:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_002397.5:c.258G>A - synonymous variant - [Sequence Ontology: SO:0001819]

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

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SRP459727 (782)
SRA
uncharacterized protein ColSpa_12229 [Colletotrichum spaethianum]
uncharacterized protein ColSpa_12229 [Colletotrichum spaethianum]
gi|2272229835|ref|XP_049134398.1|

Protein
ubiquitin-conjugating enzyme E2 32-like isoform X2 [Cucurbita pepo subsp. pepo]
ubiquitin-conjugating enzyme E2 32-like isoform X2 [Cucurbita pepo subsp. pepo]
gi|1333107758|ref|XP_023527847.1|

Protein
de69b02.x1 Kirschner embryo St10 14 Xenopus laevis cDNA clone IMAGE:3516986 3', ...
de69b02.x1 Kirschner embryo St10 14 Xenopus laevis cDNA clone IMAGE:3516986 3', mRNA sequence
gi|13314527|gnl|dbEST|8129762|gb|BG 8.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002769389	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 19, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25131622, 26633542, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002769389

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 19, 2020)

germline

clinical testing

PubMed (3)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical whole exome sequencing in child neurology practice.

Srivastava S, Cohen JS, Vernon H, Barañano K, McClellan R, Jamal L, Naidu S, Fatemi A.

Ann Neurol. 2014 Oct;76(4):473-83. doi: 10.1002/ana.24251. Epub 2014 Aug 30.

PubMed [citation]

PMID:: 25131622

Clinical application of whole-exome sequencing across clinical indications.

Retterer K, Juusola J, Cho MT, Vitazka P, Millan F, Gibellini F, Vertino-Bell A, Smaoui N, Neidich J, Monaghan KG, McKnight D, Bai R, Suchy S, Friedman B, Tahiliani J, Pineda-Alvarez D, Richard G, Brandt T, Haverfield E, Chung WK, Bale S.

Genet Med. 2016 Jul;18(7):696-704. doi: 10.1038/gim.2015.148. Epub 2015 Dec 3.

PubMed [citation]

PMID:: 26633542

See all PubMed Citations (3)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002769389.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with MEF2C-related developmental syndrome. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0212 - Non-canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0219 - This variant is non-coding in an alternative transcript. This variant is deep intronic within several RefSeq transcripts (UCSC), however it is within an exon within the transcript most highly expressed in ClinVar. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported in several patients (one confirmed de novo) with MEF2C-related haploinsufficiency syndrome (Decipher, LOVD, PMID: 25131622, PMID: 26633542). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

Last Updated: Sep 16, 2024

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