NM_001849.4(COL6A2):c.2197G>A (p.Gly733Arg) AND Bethlem myopathy 1A

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 26, 2023
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:: RCV001303665.6

Allele description [Variation Report for NM_001849.4(COL6A2):c.2197G>A (p.Gly733Arg)]

NM_001849.4(COL6A2):c.2197G>A (p.Gly733Arg)

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.2197G>A (p.Gly733Arg)

HGVS:

NC_000021.9:g.46126012G>A
NG_008675.1:g.32894G>A
NM_001849.4:c.2197G>AMANE SELECT
NM_058174.3:c.2197G>A
NM_058175.3:c.2197G>A
NP_001840.3:p.Gly733Arg
NP_001840.3:p.Gly733Arg
NP_478054.2:p.Gly733Arg
NP_478055.2:p.Gly733Arg
LRG_476t1:c.2197G>A
LRG_476:g.32894G>A
LRG_476p1:p.Gly733Arg
NC_000021.8:g.47545926G>A
NM_001849.3:c.2197G>A

Protein change:

G733R

Links:

dbSNP: rs886042922

NCBI 1000 Genomes Browser:

rs886042922

Molecular consequence:

NM_001849.4:c.2197G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_058174.3:c.2197G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_058175.3:c.2197G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001492916	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 26, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30564623, 34167565, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001492916

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 26, 2023)

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

Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients.

Nallamilli BRR, Chakravorty S, Kesari A, Tanner A, Ankala A, Schneider T, da Silva C, Beadling R, Alexander JJ, Askree SH, Whitt Z, Bean L, Collins C, Khadilkar S, Gaitonde P, Dastur R, Wicklund M, Mozaffar T, Harms M, Rufibach L, Mittal P, Hegde M.

Ann Clin Transl Neurol. 2018 Dec;5(12):1574-1587. doi: 10.1002/acn3.649.

PubMed [citation]

PMID:: 30564623
PMCID:: PMC6292381

Causative variant profile of collagen VI-related dystrophy in Japan.

Inoue M, Saito Y, Yonekawa T, Ogawa M, Iida A, Nishino I, Noguchi S.

Orphanet J Rare Dis. 2021 Jun 24;16(1):284. doi: 10.1186/s13023-021-01921-2.

PubMed [citation]

PMID:: 34167565
PMCID:: PMC8223365

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001492916.4

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 733 of the COL6A2 protein (p.Gly733Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant COL6A2-related conditions (PMID: 30564623, 34167565). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 284693). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL6A2 protein function. For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 26, 2024

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