NM_021008.4(DEAF1):c.683T>G (p.Ile228Ser) AND Intellectual disability, autosomal dominant 24

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 1, 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:: RCV000119804.5

Allele description [Variation Report for NM_021008.4(DEAF1):c.683T>G (p.Ile228Ser)]

NM_021008.4(DEAF1):c.683T>G (p.Ile228Ser)

Gene:

DEAF1:DEAF1 transcription factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_021008.4(DEAF1):c.683T>G (p.Ile228Ser)

HGVS:

NC_000011.10:g.686979A>C
NG_034156.2:g.25105T>G
NM_001293634.1:c.664+932T>G
NM_001367390.1:c.-44T>G
NM_021008.4:c.683T>GMANE SELECT
NP_066288.2:p.Ile228Ser
NC_000011.9:g.686979A>C
O75398:p.Ile228Ser

Protein change:

I228S; ILE228SER

Links:

UniProtKB: O75398#VAR_065089; OMIM: 602635.0001; dbSNP: rs587777406

NCBI 1000 Genomes Browser:

rs587777406

Molecular consequence:

NM_001367390.1:c.-44T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001293634.1:c.664+932T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_021008.4:c.683T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Intellectual disability, autosomal dominant 24 (VSVS)
Synonyms:: VULTO-VAN SILFHOUT-DE VRIES SYNDROME
Identifiers:: MONDO: MONDO:0014357; MedGen: C4014414; OMIM: 615828

Recent activity

Clear Turn Off Turn On

cytochrome oxidase subunit I, partial (mitochondrion) [Mononeuron duguetiae]
cytochrome oxidase subunit I, partial (mitochondrion) [Mononeuron duguetiae]
gi|383216574|gb|AFG73656.1|

Protein
Reevesia pycnantha isolate 160 ribulose-1,5-bisphosphate carboxylase/oxygenase l...
Reevesia pycnantha isolate 160 ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) gene, partial cds; chloroplast
gi|332015293|gb|HQ427249.1|

Nucleotide

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
SCV000154729	OMIM	no assertion criteria provided	Pathogenic (May 1, 2014)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 21076407, 24726472

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000154729

OMIM

no assertion criteria provided

Pathogenic
(May 1, 2014)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

A de novo paradigm for mental retardation.

Vissers LE, de Ligt J, Gilissen C, Janssen I, Steehouwer M, de Vries P, van Lier B, Arts P, Wieskamp N, del Rosario M, van Bon BW, Hoischen A, de Vries BB, Brunner HG, Veltman JA.

Nat Genet. 2010 Dec;42(12):1109-12. doi: 10.1038/ng.712. Epub 2010 Nov 14.

PubMed [citation]

PMID:: 21076407

Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems.

Vulto-van Silfhout AT, Rajamanickam S, Jensik PJ, Vergult S, de Rocker N, Newhall KJ, Raghavan R, Reardon SN, Jarrett K, McIntyre T, Bulinski J, Ownby SL, Huggenvik JI, McKnight GS, Rose GM, Cai X, Willaert A, Zweier C, Endele S, de Ligt J, van Bon BW, Lugtenberg D, et al.

Am J Hum Genet. 2014 May 1;94(5):649-61. doi: 10.1016/j.ajhg.2014.03.013. Epub 2014 Apr 10.

PubMed [citation]

PMID:: 24726472
PMCID:: PMC4067565

Details of each submission

From OMIM, SCV000154729.3

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

Description

In a boy with Vulto-van Silfhout-de Vries syndrome (VSVS; 615828), Vissers et al. (2010) identified a de novo heterozygous c.683T-G transversion in the DEAF1 gene, resulting in an ile228-to-ser (I228S) substitution. The mutation was found by family-based exome sequencing of 10 case-parent trios with de novo impaired intellectual development; the variant was not found in 1,664 control chromosomes.

Vulto-van Silfhout et al. (2014) noted that the I228S mutation occurs at a highly conserved residue in the SAND domain, which is essential for DNA binding. The mutation was not present in the dbSNP (build 139) or Exome Variant Server databases, or in over 2,000 in-house control exomes. In vitro functional expression studies demonstrated that the I228S mutation resulted in loss of the ability to repress the DEAF1 promoter, loss of DNA binding, loss of transcriptional activation of a reporter construct, and decreased interaction with XRCC6 (152690).

#	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

Last Updated: Aug 5, 2023

ClinVar

Relating variation to medicine