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NM_001849.4(COL6A2):c.802G>A (p.Gly268Ser) AND Bethlem myopathy 1A

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 6, 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:
RCV001951458.5

Allele description [Variation Report for NM_001849.4(COL6A2):c.802G>A (p.Gly268Ser)]

NM_001849.4(COL6A2):c.802G>A (p.Gly268Ser)

Gene:
COL6A2:collagen type VI alpha 2 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
21q22.3
Genomic location:
Preferred name:
NM_001849.4(COL6A2):c.802G>A (p.Gly268Ser)
HGVS:
  • NC_000021.9:g.46115872G>A
  • NG_008675.1:g.22754G>A
  • NM_001849.4:c.802G>AMANE SELECT
  • NM_058174.3:c.802G>A
  • NM_058175.3:c.802G>A
  • NP_001840.3:p.Gly268Ser
  • NP_478054.2:p.Gly268Ser
  • NP_478055.2:p.Gly268Ser
  • LRG_476:g.22754G>A
  • NC_000021.8:g.47535786G>A
Protein change:
G268S
Links:
dbSNP: rs2123625485
NCBI 1000 Genomes Browser:
rs2123625485
Molecular consequence:
  • NM_001849.4:c.802G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_058174.3:c.802G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_058175.3:c.802G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Bethlem myopathy 1A
Synonyms:
Myopathy, benign congenital, with contractures; Bethlem myopathy 1
Identifiers:
MONDO: MONDO:0024530; MedGen: CN029274; Orphanet: 610; OMIM: 158810

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002239692Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 6, 2022) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot 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 (8)

Details of each submission

From Invitae, SCV002239692.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the triple helix domain of COL6A2. 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 COL6A2, missense variants at these glycine residues are significantly enriched in individuals with autosomal dominant disease (PMID: 15689448, 24038877) compared to the general population (ExAC). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1460157). This missense change has been observed in individuals with autosomal dominant Bethlem myopathy (PMID: 25535305, 32053901). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 268 of the COL6A2 protein (p.Gly268Ser).

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

Last Updated: Jul 23, 2024