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NM_001849.4(COL6A2):c.855+1G>T AND Bethlem myopathy 1A

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 4, 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:
RCV002227873.2

Allele description [Variation Report for NM_001849.4(COL6A2):c.855+1G>T]

NM_001849.4(COL6A2):c.855+1G>T

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.855+1G>T
Other names:
NM_058174.3:c.855+1G>T
HGVS:
  • NC_000021.9:g.46115926G>T
  • NG_008675.1:g.22808G>T
  • NM_001849.4:c.855+1G>TMANE SELECT
  • NM_058174.3:c.855+1G>T
  • NM_058175.3:c.855+1G>T
  • LRG_476:g.22808G>T
  • NC_000021.8:g.47535840G>T
Links:
dbSNP: rs1057517988
NCBI 1000 Genomes Browser:
rs1057517988
Molecular consequence:
  • NM_001849.4:c.855+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_058174.3:c.855+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_058175.3:c.855+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV002507100Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(May 4, 2022) 		germlinecuration

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV002507100.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

The heterozygous c.855+1G>T variant in COL6A2 was identified by our study in 1 individual with Bethlem myopathy 1. Trio exome analysis showed this variant to be de novo. This variant is also reported and assumed de novo in 1 individual with Bethlem myopathy 1, but maternity and paternity have not been confirmed (PMID: 25025777), and was absent from large population studies. This variant occurs in the invariant region (+/- 1/2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Heterozygous loss of function of the COL6A2 gene is a moderately established disease mechanism in Bethlem myopathy 1. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PS2, PM2, PVS1_supporting, PS4_supporting (Richards 2015).

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

Last Updated: Jun 17, 2024