NM_001844.5(COL2A1):c.2159G>A (p.Gly720Asp) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jul 24, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000593344.2

Allele description [Variation Report for NM_001844.5(COL2A1):c.2159G>A (p.Gly720Asp)]

NM_001844.5(COL2A1):c.2159G>A (p.Gly720Asp)

Gene:
COL2A1:collagen type II alpha 1 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.11
Genomic location:
Preferred name:
NM_001844.5(COL2A1):c.2159G>A (p.Gly720Asp)
HGVS:
  • NC_000012.12:g.47982882C>T
  • NG_008072.1:g.26621G>A
  • NM_001844.5:c.2159G>AMANE SELECT
  • NM_033150.3:c.1952G>A
  • NP_001835.3:p.Gly720Asp
  • NP_149162.2:p.Gly651Asp
  • NC_000012.11:g.48376665C>T
Protein change:
G651D
Links:
dbSNP: rs1555166528
NCBI 1000 Genomes Browser:
rs1555166528
Molecular consequence:
  • NM_001844.5:c.2159G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033150.3:c.1952G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000704095EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Likely pathogenic
(Jan 6, 2017)
germlineclinical testing

Citation Link,

SCV001587073Invitaecriteria provided, single submitter
Pathogenic
(Jul 24, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical testing

Citations

PubMed

Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution.

Bella J, Eaton M, Brodsky B, Berman HM.

Science. 1994 Oct 7;266(5182):75-81.

PubMed [citation]
PMID:
7695699

Characterization of collagen-like peptides containing interruptions in the repeating Gly-X-Y sequence.

Long CG, Braswell E, Zhu D, Apigo J, Baum J, Brodsky B.

Biochemistry. 1993 Nov 2;32(43):11688-95.

PubMed [citation]
PMID:
8218237
See all PubMed Citations (6)

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000704095.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From Invitae, SCV001587073.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces glycine with aspartic acid at codon 720 of the COL2A1 protein (p.Gly720Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of COL2A1-related conditions (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 498869). Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL2A1, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 10612821, 26443184) compared to the general population (ExAC). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 14, 2021

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