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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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000154729OMIM
no assertion criteria provided
Pathogenic
(May 1, 2014) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature 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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 5, 2023