2-237344373-G-T
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_ModerateBP6BP7BS1
The NM_004369.4(COL6A3):c.7645C>A(p.Arg2549Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,614,048 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
COL6A3
NM_004369.4 synonymous
NM_004369.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.919
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 2-237344373-G-T is Benign according to our data. Variant chr2-237344373-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 284140.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=0.919 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000212 (31/1461876) while in subpopulation AFR AF= 0.000747 (25/33480). AF 95% confidence interval is 0.000519. There are 0 homozygotes in gnomad4_exome. There are 13 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| COL6A3 | NM_004369.4 | c.7645C>A | p.Arg2549Arg | synonymous_variant | Exon 36 of 44 | ENST00000295550.9 | NP_004360.2 | |
| COL6A3 | NM_057167.4 | c.7027C>A | p.Arg2343Arg | synonymous_variant | Exon 35 of 43 | NP_476508.2 | ||
| COL6A3 | NM_057166.5 | c.5824C>A | p.Arg1942Arg | synonymous_variant | Exon 33 of 41 | NP_476507.3 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000920 AC: 14AN: 152172Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
14
AN:
152172
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251268Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135854
GnomAD3 exomes
AF:
AC:
13
AN:
251268
Hom.:
AF XY:
AC XY:
4
AN XY:
135854
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727238
GnomAD4 exome
AF:
AC:
31
AN:
1461876
Hom.:
Cov.:
31
AF XY:
AC XY:
13
AN XY:
727238
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome 0.0000920 AC: 14AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74336
GnomAD4 genome
AF:
AC:
14
AN:
152172
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
74336
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Oct 29, 2015
Eurofins Ntd Llc (ga)
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Bethlem myopathy 1A Benign:1
Jan 08, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
COL6A3-related disorder Benign:1
Dec 09, 2022
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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