NM_000557.5(GDF5):c.1144del (p.Ala382fs) AND Grebe syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Dec 30, 2017
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:: RCV000761432.3

Allele description [Variation Report for NM_000557.5(GDF5):c.1144del (p.Ala382fs)]

NM_000557.5(GDF5):c.1144del (p.Ala382fs)

Genes:

GDF5-AS1:GDF5 antisense RNA 1 [Gene - HGNC]
GDF5:growth differentiation factor 5 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

20q11.22

Genomic location:

Preferred name:

NM_000557.5(GDF5):c.1144del (p.Ala382fs)

HGVS:

NC_000020.11:g.35434273del
NG_008076.3:g.25476del
NM_000557.5:c.1144delMANE SELECT
NM_001319138.2:c.1144del
NP_000548.2:p.Ala382fs
NP_001306067.1:p.Ala382fs
NC_000020.10:g.34022069del
NC_000020.10:g.34022071del
NM_000557.2:c.1144del
NM_000557.4:c.1144delG
NR_161326.1:n.557del

Note:

ClinGen staff contributed the HGVS expression for this variant.

Protein change:

A382fs

Links:

OMIM: 601146.0007; dbSNP: rs1568731526

NCBI 1000 Genomes Browser:

rs1568731526

Molecular consequence:

NM_000557.5:c.1144del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001319138.2:c.1144del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_161326.1:n.557del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Grebe syndrome
Synonyms:: Acromesomelic dysplasia, Grebe type; Brazilian achondrogenesis; Grebe dysplasia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008703; MedGen: C0265260; Orphanet: 2098; OMIM: 200700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000029100	OMIM	no assertion criteria provided	Pathogenic (Aug 15, 2003)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000891513	Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University	no assertion criteria provided	Likely pathogenic (Dec 30, 2017)	unknown	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000029100

OMIM

no assertion criteria provided

Pathogenic
(Aug 15, 2003)

germline

literature only

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

SCV000891513

Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University

no assertion criteria provided

Likely pathogenic
(Dec 30, 2017)

unknown

curation

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	unknown	yes	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Clinical and molecular analysis of Grebe acromesomelic dysplasia in an Omani family.

Al-Yahyaee SA, Al-Kindi MN, Habbal O, Kumar DS.

Am J Med Genet A. 2003 Aug 15;121A(1):9-14.

PubMed [citation]

PMID:: 12900894

Details of each submission

From OMIM, SCV000029100.1

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

Description

In 4 sibs with Grebe type acromesomelic dysplasia (200700) from an Omani family, Al-Yahyaee et al. (2003) identified 2 mutations in the GDF5 gene: a silent 1137A-G transition encoding lysine and a 1-bp deletion, 1144delG, predicting a frameshift resulting in loss of the biologically active C terminus of the protein. The affected sibs were homozygous for the 1144delG mutation and each parent was heterozygous. The affected sibs had normal axial skeletons, severely shortened and deformed limbs with severity increasing in a proximodistal gradient, and subluxated joints. The humeri and femora were hypoplastic with distal malformations. The radii/ulnae were shortened and deformed whereas carpal bones were invariably rudimentary or absent. The tibiae appeared rudimentary; fibulae were absent in 2 children, and some tarsal and metatarsal bones were absent. Only distal phalanges were present. The father and mother had short first metacarpal and middle phalanx of the fifth finger and hallux valgus, respectively.

#	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 Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University, SCV000891513.1

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

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

Last Updated: Feb 20, 2024

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