2-237324348-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate
The NM_004369.4(COL6A3):c.*426G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000975 in 164,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00034 ( 0 hom. )
Consequence
COL6A3
NM_004369.4 3_prime_UTR
NM_004369.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.22
Publications
0 publications found
Genes affected
COL6A3 (HGNC:2213): (collagen type VI alpha 3 chain) This gene encodes the alpha-3 chain, one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The alpha-3 chain of type VI collagen is much larger than the alpha-1 and -2 chains. This difference in size is largely due to an increase in the number of subdomains, similar to von Willebrand Factor type A domains, that are found in the amino terminal globular domain of all the alpha chains. These domains have been shown to bind extracellular matrix proteins, an interaction that explains the importance of this collagen in organizing matrix components. Mutations in the type VI collagen genes are associated with Bethlem myopathy, a rare autosomal dominant proximal myopathy with early childhood onset. Mutations in this gene are also a cause of Ullrich congenital muscular dystrophy, also referred to as Ullrich scleroatonic muscular dystrophy, an autosomal recessive congenital myopathy that is more severe than Bethlem myopathy. Multiple transcript variants have been identified, but the full-length nature of only some of these variants has been described. [provided by RefSeq, Jun 2009]
COL6A3 Gene-Disease associations (from GenCC):
- Bethlem myopathy 1AInheritance: AD, AR, SD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics
- collagen 6-related myopathyInheritance: AD, AR Classification: DEFINITIVE Submitted by: ClinGen
- Ullrich congenital muscular dystrophy 1CInheritance: AR Classification: DEFINITIVE Submitted by: G2P
- dystonia 27Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Illumina, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet
- Ullrich congenital muscular dystrophy 1AInheritance: AR, AD, SD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
- Bethlem myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Ullrich congenital muscular dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BP6
Variant 2-237324348-C-T is Benign according to our data. Variant chr2-237324348-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 335092.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.*426G>A | 3_prime_UTR_variant | Exon 44 of 44 | ENST00000295550.9 | NP_004360.2 | ||
COL6A3 | NM_057167.4 | c.*426G>A | 3_prime_UTR_variant | Exon 43 of 43 | NP_476508.2 | |||
COL6A3 | NM_057166.5 | c.*426G>A | 3_prime_UTR_variant | Exon 41 of 41 | NP_476507.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152140Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
12
AN:
152140
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
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Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.000336 AC: 4AN: 11910Hom.: 0 Cov.: 0 AF XY: 0.000323 AC XY: 2AN XY: 6198 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
11910
Hom.:
Cov.:
0
AF XY:
AC XY:
2
AN XY:
6198
show subpopulations
African (AFR)
AF:
AC:
0
AN:
420
American (AMR)
AF:
AC:
0
AN:
1722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
260
East Asian (EAS)
AF:
AC:
1
AN:
798
South Asian (SAS)
AF:
AC:
0
AN:
998
European-Finnish (FIN)
AF:
AC:
0
AN:
354
Middle Eastern (MID)
AF:
AC:
0
AN:
38
European-Non Finnish (NFE)
AF:
AC:
3
AN:
6810
Other (OTH)
AF:
AC:
0
AN:
510
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74434 show subpopulations
GnomAD4 genome
AF:
AC:
12
AN:
152258
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
74434
show subpopulations
African (AFR)
AF:
AC:
4
AN:
41562
American (AMR)
AF:
AC:
0
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
1
AN:
5180
South Asian (SAS)
AF:
AC:
0
AN:
4814
European-Finnish (FIN)
AF:
AC:
0
AN:
10596
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
7
AN:
68024
Other (OTH)
AF:
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.471
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Collagen 6-related myopathy Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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