NM_001913.5(CUX1):c.61C>T (p.Gln21Ter) AND Global developmental delay with or without impaired intellectual development

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Aug 31, 2018
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:: RCV000757901.12

Allele description [Variation Report for NM_001913.5(CUX1):c.61C>T (p.Gln21Ter)]

NM_001913.5(CUX1):c.61C>T (p.Gln21Ter)

Gene:

CUX1:cut like homeobox 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q22.1

Genomic location:

Preferred name:

NM_001913.5(CUX1):c.61C>T (p.Gln21Ter)

HGVS:

NC_000007.14:g.101816091C>T
NG_029476.2:g.5188C>T
NG_112027.2:g.371C>T
NM_001202543.2:c.61C>T
NM_001202544.3:c.61C>T
NM_001202545.3:c.61C>T
NM_001202546.3:c.61C>T
NM_001913.5:c.61C>T
NM_181500.4:c.61C>T
NP_001189472.1:p.Gln21Ter
NP_001189473.1:p.Gln21Ter
NP_001189474.1:p.Gln21Ter
NP_001189475.1:p.Gln21Ter
NP_001904.2:p.Gln21Ter
NP_852477.1:p.Gln21Ter
LRG_1123t2:c.61C>T
LRG_1123:g.5188C>T
LRG_1123p2:p.Gln21Ter
NC_000007.13:g.101459371C>T
NG_112027.1:g.310C>T
NM_001202543.1:c.61C>T

Protein change:

Q21*; GLN21TER

Links:

OMIM: 116896.0001; dbSNP: rs1562875556

NCBI 1000 Genomes Browser:

rs1562875556

Molecular consequence:

NM_001202543.2:c.61C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001202544.3:c.61C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001202545.3:c.61C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001202546.3:c.61C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001913.5:c.61C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_181500.4:c.61C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Global developmental delay with or without impaired intellectual development
Identifiers:: MONDO: MONDO:0032680; MedGen: C5193032; OMIM: 618330

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000886411	OMIM	no assertion criteria provided	Pathogenic (Feb 19, 2019)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001335372	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 31, 2018)	de novo	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30014507, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000886411

OMIM

no assertion criteria provided

Pathogenic
(Feb 19, 2019)

germline

literature only

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

SCV001335372

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 31, 2018)

de novo

clinical testing

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	yes	not provided	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

Haploinsufficiency of CUX1 Causes Nonsyndromic Global Developmental Delay With Possible Catch-up Development.

Platzer K, Cogné B, Hague J, Marcelis CL, Mitter D, Oberndorff K, Park SM, Ploos van Amstel HK, Simonic I, van der Smagt JJ, Stegmann APA, Stevens SJC, Stumpel CTRM, Vincent M, Lemke JR, Jamra R.

Ann Neurol. 2018 Aug;84(2):200-207. doi: 10.1002/ana.25278. Epub 2018 Aug 31.

PubMed [citation]

PMID:: 30014507

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000886411.1

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

Description

In an almost 4-year-old boy (individual 1) with global developmental delay without impaired intellectual development (GDDI; 618330), Platzer et al. (2018) identified a de novo heterozygous c.61C-T transition (c.61C-T, NM_001202543.1) in the CUX1 gene, resulting in a gln21-to-ter (Q21X) substitution. The mutation, which was found by trio exome sequencing, was absent in the gnomAD database. The boy had first speech at age 1 year, and at age 3 years 10 months was able to speak in simple sentences. He had an IQ of 94. He had motor delay with first walking at age 42 months. At the time of report he used a wheelchair for distances greater than 100 meters. He had a broad forehead and long palpebral fissures. Brain MRI showed widened right ventricle and slightly prominent fourth ventricle. He had hypotonia, pulmonary sequestration, and pectus excavatum.

#	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, SCV001335372.1

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

Description

This variant was identified as de novo (maternity and paternity confirmed).

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

Last Updated: Oct 8, 2024

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