NM_005902.4(SMAD3):c.741_742del (p.Phe248fs) AND Aneurysm-osteoarthritis syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 1, 2011
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:: RCV000023242.4

Allele description [Variation Report for NM_005902.4(SMAD3):c.741_742del (p.Phe248fs)]

NM_005902.4(SMAD3):c.741_742del (p.Phe248fs)

Gene:

SMAD3:SMAD family member 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q22.33

Genomic location:

Preferred name:

NM_005902.4(SMAD3):c.741_742del (p.Phe248fs)

HGVS:

NC_000015.10:g.67181323_67181324del
NG_011990.1:g.120467_120468del
NM_001145102.2:c.426_427del
NM_001145103.2:c.609_610del
NM_001145104.2:c.156_157del
NM_005902.4:c.741_742delMANE SELECT
NP_001138574.1:p.Phe143fs
NP_001138575.1:p.Phe204fs
NP_001138576.1:p.Phe53fs
NP_005893.1:p.Phe248fs
NC_000015.9:g.67473661_67473662del
NM_005902.3:c.741_742del

Protein change:

F143fs

Links:

OMIM: 603109.0002; dbSNP: rs587776880

NCBI 1000 Genomes Browser:

rs587776880

Molecular consequence:

NM_001145102.2:c.426_427del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001145103.2:c.609_610del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001145104.2:c.156_157del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005902.4:c.741_742del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Aneurysm-osteoarthritis syndrome
Synonyms:: ANEURYSMS-OSTEOARTHRITIS SYNDROME; LOEYS-DIETZ SYNDROME WITH OSTEOARTHRITIS; Loeys-Dietz syndrome 3; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013426; MedGen: C3151087; Orphanet: 284984; OMIM: 613795

Recent activity

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Propionibacterium freudenreichii strain FAM19033 D-glycerate dehydrogenase, clas...
Propionibacterium freudenreichii strain FAM19033 D-glycerate dehydrogenase, class II fumarate hydratase (fumC), hypothetical protein, aspartate ammonia-lyase (aspA), and ISL3-like element ISPfr1 family transposase genes, complete cds; anaerobic C4-dicarboxylate transporter (dcuA) gene, partial sequence; aspartate/glutamate racemase family protein gene, complete cds; and MFS transporter pseudogene, partial sequence
gi|2220784727|gb|OK490971.1|

Nucleotide
Bacillus subtilis strain HGB126 16S ribosomal RNA gene, partial sequence
Bacillus subtilis strain HGB126 16S ribosomal RNA gene, partial sequence
gi|1137166597|gb|KX280633.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000044533	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2011)	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

SCV000044533

OMIM

no assertion criteria provided

Pathogenic
(Feb 1, 2011)

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

Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis.

van de Laar IM, Oldenburg RA, Pals G, Roos-Hesselink JW, de Graaf BM, Verhagen JM, Hoedemaekers YM, Willemsen R, Severijnen LA, Venselaar H, Vriend G, Pattynama PM, Collée M, Majoor-Krakauer D, Poldermans D, Frohn-Mulder IM, Micha D, Timmermans J, Hilhorst-Hofstee Y, Bierma-Zeinstra SM, Willems PJ, Kros JM, et al.

Nat Genet. 2011 Feb;43(2):121-6. doi: 10.1038/ng.744. Epub 2011 Jan 9.

PubMed [citation]

PMID:: 21217753

Details of each submission

From OMIM, SCV000044533.3

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

Description

In 3 Dutch sibs with arterial aneurysms and dissections and early-onset osteoarthritis (LDS3; 613795), van de Laar et al. (2011) identified heterozygosity for a 2-bp deletion (741delAT) in exon 6 of the SMAD3 gene, resulting in a frameshift and a premature termination sequence at codon 309 in exon 7 that removes nearly the complete MH2 domain (Thr247ProfsTer61). The deletion, which was presumably present in their affected deceased father, was not found in their unaffected mother or in 544 Dutch control chromosomes. Analysis of patient cDNA showed very weak mutant signal compared to wildtype, and treatment of patient fibroblast cultures with cycloheximide markedly increased the mutant signal, indicating that most of the abnormal RNA was subjected to nonsense messenger RNA decay and that a truncated SMAD3 protein was barely formed.

#	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: Nov 5, 2022

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