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NM_198239.2(CCN6):c.737T>C (p.Leu246Pro) AND Metaphyseal chondrodysplasia, Schmid type

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 21, 2024
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:
RCV004527115.1

Allele description

NM_198239.2(CCN6):c.737T>C (p.Leu246Pro)

Gene:
CCN6:cellular communication network factor 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6q21
Genomic location:
Preferred name:
NM_198239.2(CCN6):c.737T>C (p.Leu246Pro)
HGVS:
  • NC_000006.12:g.112068352T>C
  • NG_011748.1:g.19278T>C
  • NM_003880.4:c.737T>C
  • NM_198239.2:c.737T>CMANE SELECT
  • NP_003871.1:p.Leu246Pro
  • NP_937882.2:p.Leu246Pro
  • NC_000006.11:g.112389555T>C
  • NR_125353.2:n.1055T>C
  • NR_125354.3:n.882T>C
Protein change:
L246P
Molecular consequence:
  • NM_003880.4:c.737T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198239.2:c.737T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_125353.2:n.1055T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_125354.3:n.882T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Metaphyseal chondrodysplasia, Schmid type (MCDS)
Synonyms:
SPONDYLOMETAPHYSEAL DYSPLASIA, JAPANESE TYPE
Identifiers:
MONDO: MONDO:0007983; MedGen: C0265289; Orphanet: 174; OMIM: 156500

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005039617Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Mar 21, 2024) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Clinical and molecular characterization in a cohort of patients with progressive pseudorheumatoid dysplasia.

El Dessouki D, Amr K, Kholoussi N, Rady HM, Temtamy SA, Abdou MMS, Aglan M.

Am J Med Genet A. 2023 Sep;191(9):2329-2336. doi: 10.1002/ajmg.a.63339. Epub 2023 Jun 28.

PubMed [citation]
PMID:
37377052

Specific early signs and long-term follow-up findings of progressive pseudorheumatoid dysplasia (PPRD) in the Turkish cohort.

Uludağ Alkaya D, Kasapçopur Ö, Bursalı A, Adrovic A, Demir B, Aykut A, Tüysüz B.

Rheumatology (Oxford). 2022 Aug 30;61(9):3693-3703. doi: 10.1093/rheumatology/keab926.

PubMed [citation]
PMID:
34919662

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005039617.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: COL10A1 c.737T>C (p.Ile246Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 251246 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in COL10A1 causing Metaphyseal Chondrodysplasia, Schmid Type (4.4e-05 vs ND), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.737T>C in individuals affected with Metaphyseal Chondrodysplasia, Schmid Type and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 7, 2024