2-237324810-G-A
Variant names:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_004369.4(COL6A3):c.9498C>T(p.Leu3166Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,613,470 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 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
COL6A3
NM_004369.4 synonymous
NM_004369.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.605
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 2-237324810-G-A is Benign according to our data. Variant chr2-237324810-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 287183.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.605 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000263 (40/152226) while in subpopulation AFR AF= 0.000963 (40/41524). AF 95% confidence interval is 0.000727. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| COL6A3 | NM_004369.4 | c.9498C>T | p.Leu3166Leu | synonymous_variant | Exon 44 of 44 | ENST00000295550.9 | NP_004360.2 | |
| COL6A3 | NM_057167.4 | c.8880C>T | p.Leu2960Leu | synonymous_variant | Exon 43 of 43 | NP_476508.2 | ||
| COL6A3 | NM_057166.5 | c.7677C>T | p.Leu2559Leu | synonymous_variant | Exon 41 of 41 | NP_476507.3 |
Ensembl
Frequencies
GnomAD3 genomes 0.000263 AC: 40AN: 152108Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000685 AC: 17AN: 248108Hom.: 0 AF XY: 0.0000521 AC XY: 7AN XY: 134294
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461244Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25AN XY: 726876
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GnomAD4 genome 0.000263 AC: 40AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74428
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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
Mar 29, 2016
Eurofins Ntd Llc (ga)
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Bethlem myopathy 1A Benign:1
Aug 15, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
COL6A3-related disorder Benign:1
Aug 13, 2019
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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at