NM_006565.4(CTCF):c.1186dup (p.Arg396fs) AND Intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 21, 2019
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:: RCV000074334.5

Allele description [Variation Report for NM_006565.4(CTCF):c.1186dup (p.Arg396fs)]

NM_006565.4(CTCF):c.1186dup (p.Arg396fs)

Gene:

CTCF:CCCTC-binding factor [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

16q22.1

Genomic location:

Preferred name:

NM_006565.4(CTCF):c.1186dup (p.Arg396fs)

HGVS:

NC_000016.10:g.67620796dup
NG_033892.1:g.63390dup
NM_001191022.2:c.202dup
NM_001363916.1:c.1186dup
NM_006565.4:c.1186dupMANE SELECT
NP_001177951.1:p.Arg68fs
NP_001350845.1:p.Arg396fs
NP_006556.1:p.Arg396fs
NC_000016.9:g.67654699dup
NM_006565.3:c.1186dup
NM_006565.3:c.1186dupA

Protein change:

R396fs

Links:

OMIM: 604167.0002; dbSNP: rs879255571

NCBI 1000 Genomes Browser:

rs879255571

Molecular consequence:

NM_001191022.2:c.202dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001363916.1:c.1186dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006565.4:c.1186dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome (MRD21)
Synonyms:: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 21
Identifiers:: MONDO: MONDO:0014213; MedGen: C3809686; Orphanet: 363611; OMIM: 615502

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000105940	OMIM	no assertion criteria provided	Pathogenic (Jul 11, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002026312	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 21, 2019)	de novo	research	PubMed (2) [See all records that cite these PMIDs] 31239556, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000105940

OMIM

no assertion criteria provided

Pathogenic
(Jul 11, 2013)

germline

literature only

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

SCV002026312

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 21, 2019)

de novo

research

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	de novo	unknown	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

De novo mutations in the genome organizer CTCF cause intellectual disability.

Gregor A, Oti M, Kouwenhoven EN, Hoyer J, Sticht H, Ekici AB, Kjaergaard S, Rauch A, Stunnenberg HG, Uebe S, Vasileiou G, Reis A, Zhou H, Zweier C.

Am J Hum Genet. 2013 Jul 11;93(1):124-31. doi: 10.1016/j.ajhg.2013.05.007. Epub 2013 Jun 6.

PubMed [citation]

PMID:: 23746550
PMCID:: PMC3710752

CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum.

Konrad EDH, Nardini N, Caliebe A, Nagel I, Young D, Horvath G, Santoro SL, Shuss C, Ziegler A, Bonneau D, Kempers M, Pfundt R, Legius E, Bouman A, Stuurman KE, Õunap K, Pajusalu S, Wojcik MH, Vasileiou G, Le Guyader G, Schnelle HM, Berland S, et al.

Genet Med. 2019 Dec;21(12):2723-2733. doi: 10.1038/s41436-019-0585-z. Epub 2019 Jun 26.

PubMed [citation]

PMID:: 31239556
PMCID:: PMC6892744

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000105940.3

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

Description

In a 9-year-old boy with borderline intelligence, microcephaly, developmental delay, pronounced learning difficulties, and behavioral problems (MRD21; 615502), Gregor et al. (2013) identified a de novo 1-bp duplication (c.1186dupA) in exon 6 of the CTCF gene, predicted to cause a frameshift resulting in a premature termination codon. Analysis of patient lymphocytes revealed reduced expression of CTCF; sequencing confirmed the almost complete absence of the mutated allele, consistent with loss of function or haploinsufficiency. The duplication was not found in the parents, in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases, in more than 1,500 in-house exomes, or in 820 healthy controls.

#	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 Institute of Human Genetics, University of Leipzig Medical Center, SCV002026312.1

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

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

Last Updated: Nov 18, 2024

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