NM_001101.5(ACTB):c.349G>A (p.Glu117Lys) AND Baraitser-Winter syndrome 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 15, 2014
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000056289.28

Allele description [Variation Report for NM_001101.5(ACTB):c.349G>A (p.Glu117Lys)]

NM_001101.5(ACTB):c.349G>A (p.Glu117Lys)

Gene:

ACTB:actin beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p22.1

Genomic location:

Preferred name:

NM_001101.5(ACTB):c.349G>A (p.Glu117Lys)

HGVS:

NC_000007.14:g.5529175C>T
NG_007992.1:g.6427G>A
NM_001101.5:c.349G>AMANE SELECT
NP_001092.1:p.Glu117Lys
LRG_132t1:c.349G>A
LRG_132:g.6427G>A
LRG_132p1:p.Glu117Lys
NC_000007.13:g.5568806C>T
NM_001101.3:c.349G>A

Protein change:

E117K; GLU117LYS

Links:

OMIM: 102630.0006; dbSNP: rs397515470

NCBI 1000 Genomes Browser:

rs397515470

Molecular consequence:

NM_001101.5:c.349G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Baraitser-Winter syndrome 1 (BRWS1)
Synonyms:: Iris coloboma with ptosis, hypertelorism, and mental retardation; BARAITSER-WINTER SYNDROME 1, ATYPICAL; PACHYGYRIA, MENTAL RETARDATION, EPILEPSY, AND CHARACTERISTIC FACIES; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009470; MedGen: C1855722; Orphanet: 2649; Orphanet: 2995; OMIM: 243310

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000087459	OMIM	no assertion criteria provided	Pathogenic (Sep 1, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000148639	Department of Genetics, Robert DEBRE University Hospital	no assertion criteria provided	Pathogenic (Apr 15, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000087459

OMIM

no assertion criteria provided

Pathogenic
(Sep 1, 2013)

germline

literature only

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

SCV000148639

Department of Genetics, Robert DEBRE University Hospital

no assertion criteria provided

Pathogenic
(Apr 15, 2014)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Functional analysis of a de novo ACTB mutation in a patient with atypical Baraitser-Winter syndrome.

Johnston JJ, Wen KK, Keppler-Noreuil K, McKane M, Maiers JL, Greiner A, Sapp JC; NIH Intramural Sequencing Center., Demali KA, Rubenstein PA, Biesecker LG.

Hum Mutat. 2013 Sep;34(9):1242-9. doi: 10.1002/humu.22350. Epub 2013 May 28.

PubMed [citation]

PMID:: 23649928
PMCID:: PMC3745514

Baraitser-Winter cerebrofrontofacial syndrome: delineation of the spectrum in 42 cases.

Verloes A, Di Donato N, Masliah-Planchon J, Jongmans M, Abdul-Raman OA, Albrecht B, Allanson J, Brunner H, Bertola D, Chassaing N, David A, Devriendt K, Eftekhari P, Drouin-Garraud V, Faravelli F, Faivre L, Giuliano F, Guion Almeida L, Juncos J, Kempers M, Eker HK, Lacombe D, et al.

Eur J Hum Genet. 2015 Mar;23(3):292-301. doi: 10.1038/ejhg.2014.95. Epub 2014 Jul 23.

PubMed [citation]

PMID:: 25052316
PMCID:: PMC4326722

Details of each submission

From OMIM, SCV000087459.1

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

Description

In a 7-year-old girl with atypical Baraitser-Winter syndrome-1 (243310), who had microcephaly, intellectual disability, and facial dysmorphism but no lissencephaly or seizures, Johnston et al. (2013) identified heterozygosity for a de novo c.349G-A transition in the ACTB gene, resulting in a glu117-to-lys (E117K) substitution. The mutation was not present in either of her unaffected parents. Patient lymphocytes demonstrated significantly decreased ability to adhere to a fibronectin-coated surface and formed few actin-rich protrusions compared to the parents' lymphocytes. Studies in yeast showed virtually complete loss of normal polarization of the cytoskeleton with the mutant, and mutant cells were almost completely resistant to the depolymerizing agent latrunculin A, suggesting that E117K might result in strengthened actin monomer-monomer interactions and increased filament stability.

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

From Department of Genetics, Robert DEBRE University Hospital, SCV000148639.1

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

#	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		1	not provided	not provided	not provided

Last Updated: Nov 25, 2023

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