NM_000493.4(COL10A1):c.1897del (p.Leu633fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 19, 2023
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:: RCV001891452.4

Allele description [Variation Report for NM_000493.4(COL10A1):c.1897del (p.Leu633fs)]

NM_000493.4(COL10A1):c.1897del (p.Leu633fs)

Genes:

NT5DC1:5'-nucleotidase domain containing 1 [Gene - HGNC]
COL10A1:collagen type X alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

6q22.1

Genomic location:

Preferred name:

NM_000493.4(COL10A1):c.1897del (p.Leu633fs)

HGVS:

NC_000006.12:g.116120220del
NG_008032.1:g.10915del
NG_021351.1:g.24385del
NG_021351.2:g.24369del
NM_000493.4:c.1897delMANE SELECT
NM_001424106.1:c.1897del
NM_001424107.1:c.1897del
NM_152729.3:c.529+2275delMANE SELECT
NP_000484.2:p.Leu633fs
NP_001411035.1:p.Leu633fs
NP_001411036.1:p.Leu633fs
NC_000006.11:g.116441382del
NC_000006.11:g.116441383del

Protein change:

L633fs

Links:

dbSNP: rs2114277437

NCBI 1000 Genomes Browser:

rs2114277437

Molecular consequence:

NM_000493.4:c.1897del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001424106.1:c.1897del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001424107.1:c.1897del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152729.3:c.529+2275del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002160570	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 19, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21447328, 33764685, 36400164, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002160570

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 19, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A novel mutation leading to elongation of the deduced α1(X) chain results in Metaphyseal Chondrodysplasia type Schmid.

Zhu Y, Li L, Zhou L, Mei H, Jin K, Liu K, Xu W, Tang J, Yang Y, Zhao R, He X.

Clin Chim Acta. 2011 Jun 11;412(13-14):1266-9. doi: 10.1016/j.cca.2011.03.026. Epub 2011 Apr 5.

PubMed [citation]

PMID:: 21447328

Characterization of a novel COL10A1 variant associated with Schmid-type metaphyseal chondrodysplasia and a literature review.

Wu H, Wang S, Li G, Yao Y, Wang N, Sun X, Fang L, Jiang X, Zhao J, Wang Y, Xu C.

Mol Genet Genomic Med. 2021 May;9(5):e1668. doi: 10.1002/mgg3.1668. Epub 2021 Mar 25. Review.

PubMed [citation]

PMID:: 33764685
PMCID:: PMC8172203

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002160570.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Leu633Trpfs*44) in the COL10A1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acid(s) of the COL10A1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of autosomal dominant metaphyseal chondrodysplasia, Schmid type (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1395717). This variant is located in a region of the COL10A1 protein where a significant number of COL10A1 nonsense and frameshift mutations have been reported in association with autosomal dominant metaphyseal chondrodysplasia (PMID: 21447328, 33764685, 36400164). For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

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