NM_000493.4(COL10A1):c.1955T>C (p.Leu652Pro) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 21, 2022
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:: RCV002949110.2

Allele description [Variation Report for NM_000493.4(COL10A1):c.1955T>C (p.Leu652Pro)]

NM_000493.4(COL10A1):c.1955T>C (p.Leu652Pro)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

6q22.1

Genomic location:

Preferred name:

NM_000493.4(COL10A1):c.1955T>C (p.Leu652Pro)

HGVS:

NC_000006.12:g.116120161A>G
NG_008032.1:g.10973T>C
NG_021351.1:g.24326A>G
NG_021351.2:g.24310A>G
NM_000493.4:c.1955T>CMANE SELECT
NM_001424106.1:c.1955T>C
NM_001424107.1:c.1955T>C
NM_152729.3:c.529+2216A>GMANE SELECT
NP_000484.2:p.Leu652Pro
NP_001411035.1:p.Leu652Pro
NP_001411036.1:p.Leu652Pro
NC_000006.11:g.116441324A>G

Protein change:

L652P

Molecular consequence:

NM_152729.3:c.529+2216A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000493.4:c.1955T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001424106.1:c.1955T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001424107.1:c.1955T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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3'-5' exonuclease (plasmid) [Escherichia coli]
3'-5' exonuclease (plasmid) [Escherichia coli]
gi|1566446414|gnl|PRJNA508823|EJC48 0|gb|QAZ79859.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003278583	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 21, 2022)	germline	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

SCV003278583

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 21, 2022)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003278583.2

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 652 of the COL10A1 protein (p.Leu652Pro). This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with clinical features of metaphysical chondrodysplasia (Invitae). In at least one individual the variant was observed to be de novo.

#	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 1, 2024

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