NM_002427.4(MMP13):c.619T>G (p.Trp207Gly) AND Metaphyseal chondrodysplasia, Spahr type

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 10, 2020
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:: RCV000162347.5

Allele description [Variation Report for NM_002427.4(MMP13):c.619T>G (p.Trp207Gly)]

NM_002427.4(MMP13):c.619T>G (p.Trp207Gly)

Gene:

MMP13:matrix metallopeptidase 13 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q22.2

Genomic location:

Preferred name:

NM_002427.4(MMP13):c.619T>G (p.Trp207Gly)

HGVS:

NC_000011.10:g.102954174A>C
NG_021404.1:g.6561T>G
NM_002427.4:c.619T>GMANE SELECT
NP_002418.1:p.Trp207Gly
NC_000011.9:g.102824903A>C
NM_002427.3:c.619T>G
P45452:p.Trp207Gly

Protein change:

W207G; TRP207GLY

Links:

UniProtKB: P45452#VAR_073418; OMIM: 600108.0005; dbSNP: rs140059558

NCBI 1000 Genomes Browser:

rs140059558

Molecular consequence:

NM_002427.4:c.619T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Metaphyseal chondrodysplasia, Spahr type (MDST)
Identifiers:: MONDO: MONDO:0009597; MedGen: C0432225; OMIM: 250400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000212650	OMIM	no assertion criteria provided	Pathogenic (May 1, 2014)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 13915518, 24648384
SCV000854742	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	no assertion criteria provided	Pathogenic (Jun 6, 2018)	germline	clinical testing
SCV001524343	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 10, 2020)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000212650

OMIM

no assertion criteria provided

Pathogenic
(May 1, 2014)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000854742

Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City

no assertion criteria provided

Pathogenic
(Jun 6, 2018)

germline

clinical testing

SCV001524343

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 10, 2020)

unknown

clinical testing

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	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

[Familial metaphysial dysostosis. Study of 4 cases in siblings].

SPAHR A, SPAHR-HARTMANN I.

Helv Paediatr Acta. 1961 Dec;16:836-49. French. No abstract available.

PubMed [citation]

PMID:: 13915518

MMP13 mutations are the cause of recessive metaphyseal dysplasia, Spahr type.

Bonafé L, Liang J, Gorna MW, Zhang Q, Ha-Vinh R, Campos-Xavier AB, Unger S, Beckmann JS, Le Béchec A, Stevenson B, Giedion A, Liu X, Superti-Furga G, Wang W, Spahr A, Superti-Furga A.

Am J Med Genet A. 2014 May;164A(5):1175-9. doi: 10.1002/ajmg.a.36431. Epub 2014 Mar 19.

PubMed [citation]

PMID:: 24648384

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000212650.2

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

Description

In 2 affected members of the Swiss family with Spahr type metaphyseal dysplasia (MDST; 250400), originally described by Spahr and Spahr-Hartmann (1961), Bonafe et al. (2014) identified homozygosity for a c.619T-G transversion in the MMP13 gene, resulting in a trp207-to-gly (W207G) substitution at a highly conserved residue in the core of the catalytic domain. The mutation, which was present in heterozygosity in all obligate carriers in the family, was not found in 100 local controls; however, it was detected in 2 of approximately 13,000 unselected alleles in the Exome Variant Server database, for an allelic frequency of approximately 0.00015, which the authors stated was in the range of a very rare recessive allele.

#	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 Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City, SCV000854742.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	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 Baylor Genetics, SCV001524343.1

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

Description

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

#	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: Sep 29, 2024

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