NM_001159773.2(CANT1):c.902_906dup (p.Ser303fs) AND Desbuquois dysplasia 1

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Mar 25, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000024005.16

Allele description [Variation Report for NM_001159773.2(CANT1):c.902_906dup (p.Ser303fs)]

NM_001159773.2(CANT1):c.902_906dup (p.Ser303fs)

Gene:

CANT1:calcium activated nucleotidase 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_001159773.2(CANT1):c.902_906dup (p.Ser303fs)

HGVS:

NC_000017.10:g.76989931_76989932insGGCGC
NC_000017.11:g.78993853GCGGC[3]
NG_016645.1:g.20959GCGCC[3]
NM_001159772.2:c.902_906dup
NM_001159773.2:c.902_906dupMANE SELECT
NM_138793.3:c.902_906dup5
NM_138793.4:c.902_906dup
NP_001153244.1:p.Ser303fs
NP_001153245.1:p.Ser303fs
NP_620148.1:p.Ser303fs
NC_000017.10:g.76989931_76989932insGGCGC
NC_000017.10:g.76989932_76989936dup
NC_000017.10:g.76989935GCGGC[3]
NM_001159772.1:c.893_894insGCCGC
NM_001159772.1:c.902_906dup
NM_001159773.2:c.902_906dup
NM_001159773.2:c.906_907insGCGCCMANE SELECT
NM_138793.3:c.902_906dup
NM_138793.3:c.902_906dup5
NM_138793.3:c.902_906dupGCGCC

Protein change:

S303fs

Links:

OMIM: 613165.0008; dbSNP: rs587776895

NCBI 1000 Genomes Browser:

rs587776895

Molecular consequence:

NM_001159772.2:c.902_906dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001159773.2:c.902_906dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_138793.4:c.902_906dup - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Desbuquois dysplasia 1 (DBQD1)
Synonyms:: MICROMELIC DWARFISM WITH VERTEBRAL AND METAPHYSEAL ABNORMALITIES AND ADVANCED CARPOTARSAL OSSIFICATION; DESBUQUOIS DYSPLASIA 1, KIM VARIANT
Identifiers:: MONDO: MONDO:0009629; MedGen: C4012146; Orphanet: 1425; OMIM: 251450

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000045296	OMIM	no assertion criteria provided	Pathogenic (May 1, 2010)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001426589	Centogene AG - the Rare Disease Company	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 32860008
SCV001870447	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	no assertion criteria provided	Pathogenic (Apr 29, 2021)	germline	research
SCV002072475	Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital	no assertion criteria provided	Pathogenic (Jan 30, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004805417	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 25, 2024)	germline	research	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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	research
South East Asian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation of CANT1 causes Desbuquois dysplasia.

Faden M, Al-Zahrani F, Arafah D, Alkuraya FS.

Am J Med Genet A. 2010 May;152A(5):1157-60. doi: 10.1002/ajmg.a.33404.

PubMed [citation]

PMID:: 20425819

Successful application of genome sequencing in a diagnostic setting: 1007 index cases from a clinically heterogeneous cohort.

Bertoli-Avella AM, Beetz C, Ameziane N, Rocha ME, Guatibonza P, Pereira C, Calvo M, Herrera-Ordonez N, Segura-Castel M, Diego-Alvarez D, Zawada M, Kandaswamy KK, Werber M, Paknia O, Zielske S, Ugrinovski D, Warnack G, Kampe K, Iurașcu MI, Cozma C, Vogel F, Alhashem A, et al.

Eur J Hum Genet. 2021 Jan;29(1):141-153. doi: 10.1038/s41431-020-00713-9. Epub 2020 Aug 28.

PubMed [citation]

PMID:: 32860008
PMCID:: PMC7852664

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000045296.4

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

Description

In a male infant, born of consanguineous Saudi Arabian parents, with Desbuquois dysplasia-1 (DBQD1; 251450), Faden et al. (2010) identified a homozygous 5-bp duplication (893_894insGCCGC) in exon 4 of the CANT1 gene, resulting in a frameshift and premature termination of the protein at codon 325. The patient had micromelia, severe growth retardation, clubfeet, dysmorphic facial features, hypotonia, short neck, widely spaced nipples, and protuberant abdomen. Radiographs showed typical hand findings with 2 supernumerary ossification centers and phalangeal dislocations, vertebral bodies with coronal clefting, and spur-like projections in the lesser trochanters. He also had bilateral congenital glaucoma. Three older sibs had died in the neonatal period of a similar disorder.

#	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 Centogene AG - the Rare Disease Company, SCV001426589.1

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

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

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV001870447.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	not provided

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

From Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, SCV002072475.1

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

Description

The homozygous frameshift insertion variant c.906_907insGCGCC (p.S303Afs*20) has been previously reported by Huber C et al in 2009 in a Moroccan patient. The allele frequency is 0.0008% in gnomAD (aggregated) database. In-silico bioinformatic software predict this variant by mutation taster as Disease causing. The phenotype observed was micromelia, monkey wrench feature. Desbuquois Dysplasia 1 is an autosomal recessive disorder. Based on the phenotypic observation, we classify this variant as pathogenic.

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

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004805417.2

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

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

Last Updated: Oct 26, 2024

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