NM_001849.4(COL6A2):c.2002G>T (p.Glu668Ter) AND Bethlem myopathy 1A

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 29, 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:: RCV000537082.5

Allele description [Variation Report for NM_001849.4(COL6A2):c.2002G>T (p.Glu668Ter)]

NM_001849.4(COL6A2):c.2002G>T (p.Glu668Ter)

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.2002G>T (p.Glu668Ter)

HGVS:

NC_000021.9:g.46125817G>T
NG_008675.1:g.32699G>T
NM_001849.4:c.2002G>TMANE SELECT
NM_058174.3:c.2002G>T
NM_058175.3:c.2002G>T
NP_001840.3:p.Glu668Ter
NP_001840.3:p.Glu668Ter
NP_478054.2:p.Glu668Ter
NP_478055.2:p.Glu668Ter
LRG_476t1:c.2002G>T
LRG_476:g.32699G>T
LRG_476p1:p.Glu668Ter
NC_000021.8:g.47545731G>T
NM_001849.3:c.2002G>T

Protein change:

E668*

Links:

dbSNP: rs138948335

NCBI 1000 Genomes Browser:

rs138948335

Molecular consequence:

NM_001849.4:c.2002G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_058174.3:c.2002G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_058175.3:c.2002G>T - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000657129	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 29, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19884007, 20976770, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000657129

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 29, 2022)

germline

clinical testing

PubMed (3)
[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

Autosomal recessive inheritance of classic Bethlem myopathy.

Foley AR, Hu Y, Zou Y, Columbus A, Shoffner J, Dunn DM, Weiss RB, Bönnemann CG.

Neuromuscul Disord. 2009 Dec;19(12):813-7. doi: 10.1016/j.nmd.2009.09.010. Epub 2009 Nov 1.

PubMed [citation]

PMID:: 19884007
PMCID:: PMC2787906

Early onset collagen VI myopathies: Genetic and clinical correlations.

Briñas L, Richard P, Quijano-Roy S, Gartioux C, Ledeuil C, Lacène E, Makri S, Ferreiro A, Maugenre S, Topaloglu H, Haliloglu G, Pénisson-Besnier I, Jeannet PY, Merlini L, Navarro C, Toutain A, Chaigne D, Desguerre I, de Die-Smulders C, Dunand M, Echenne B, Eymard B, et al.

Ann Neurol. 2010 Oct;68(4):511-20. doi: 10.1002/ana.22087.

PubMed [citation]

PMID:: 20976770

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000657129.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 476462). This variant has not been reported in the literature in individuals affected with COL6A2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu668*) in the COL6A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL6A2 are known to be pathogenic (PMID: 19884007, 20976770).

#	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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