NM_016474.5(CCDC174):c.1404A>G (p.Ter468Trp) AND Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 18, 2016
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:: RCV000207515.1

Allele description [Variation Report for NM_016474.5(CCDC174):c.1404A>G (p.Ter468Trp)]

NM_016474.5(CCDC174):c.1404A>G (p.Ter468Trp)

Genes:

LOC126806614:BRD4-independent group 4 enhancer GRCh37_chr3:14712491-14713690 [Gene]
CCDC174:coiled-coil domain containing 174 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_016474.5(CCDC174):c.1404A>G (p.Ter468Trp)

Other names:

*468W

HGVS:

NC_000003.12:g.14671194A>G
NG_046773.1:g.24449A>G
NM_016474.5:c.1404A>GMANE SELECT
NP_057558.3:p.Ter468Trp
NC_000003.11:g.14712701A>G
NM_016474.4:c.1404A>G
NR_135523.2:n.1384A>G

Nucleotide change:

1404A-G

Links:

OMIM: 616735.0001; dbSNP: rs869025342

NCBI 1000 Genomes Browser:

rs869025342

Molecular consequence:

NR_135523.2:n.1384A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_016474.5:c.1404A>G - stop lost - [Sequence Ontology: SO:0001578]

Condition(s)

Name:: Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome
Synonyms:: Hypotonia, infantile, with psychomotor retardation
Identifiers:: MONDO: MONDO:0014784; MedGen: C4225196; OMIM: 616816

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000263071	OMIM	no assertion criteria provided	Pathogenic (Feb 18, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000263071

OMIM

no assertion criteria provided

Pathogenic
(Feb 18, 2016)

germline

literature only

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

Citations

PubMed

CDC174, a novel component of the exon junction complex whose mutation underlies a syndrome of hypotonia and psychomotor developmental delay.

Volodarsky M, Lichtig H, Leibson T, Sadaka Y, Kadir R, Perez Y, Liani-Leibson K, Gradstein L, Shaco-Levy R, Shorer Z, Frank D, Birk OS.

Hum Mol Genet. 2015 Nov 15;24(22):6485-91. doi: 10.1093/hmg/ddv357. Epub 2015 Sep 10.

PubMed [citation]

PMID:: 26358778

Details of each submission

From OMIM, SCV000263071.1

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

Description

In 6 patients from 2 unrelated families, 1 of Jewish Ethiopian descent and another of Israeli Arab Bedouin descent, with infantile hypotonia with psychomotor retardation (IHPMR; 616816), Volodarsky et al. (2015) identified a homozygous c.1404A-G transition (c.1404A-G, NM_016474.4) in the CCDC164 gene, predicted to extend the protein by 6 additional residues (Ter468TrpextTer6). The mutation, which was found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in both families and was not found in 400 Bedouin controls. It was found in heterozygous state in 1 of 100 Jewish Ethiopian control individuals. Haplotype analysis suggested a founder effect for the 2 families. Expression of the mutation into ccdc174-null Xenopus oocytes was unable to rescue the neural defect, consistent with a loss of function. Mutant CCDC174 localized normally to the nucleus and was able to interact with EIF4A3, but overexpression of mutant CCDC174 resulted in rapid and massive apoptosis of cells and aggregation of the mutant protein in the nucleus.

#	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: Oct 14, 2023

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