rs35902696
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_004369.4(COL6A3):āc.7086A>Cā(p.Gly2362=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 1,613,940 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.018 ( 107 hom., cov: 32)
Exomes š: 0.0023 ( 95 hom. )
Consequence
COL6A3
NM_004369.4 synonymous
NM_004369.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.424
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 2-237346509-T-G is Benign according to our data. Variant chr2-237346509-T-G is described in ClinVar as [Benign]. Clinvar id is 94978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237346509-T-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.424 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0606 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A3 | NM_004369.4 | c.7086A>C | p.Gly2362= | synonymous_variant | 32/44 | ENST00000295550.9 | |
COL6A3 | NM_057167.4 | c.6468A>C | p.Gly2156= | synonymous_variant | 31/43 | ||
COL6A3 | NM_057166.5 | c.5265A>C | p.Gly1755= | synonymous_variant | 29/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A3 | ENST00000295550.9 | c.7086A>C | p.Gly2362= | synonymous_variant | 32/44 | 1 | NM_004369.4 | P1 | |
COL6A3 | ENST00000472056.5 | c.5265A>C | p.Gly1755= | synonymous_variant | 29/41 | 1 | |||
COL6A3 | ENST00000353578.9 | c.6468A>C | p.Gly2156= | synonymous_variant | 31/43 | 5 | |||
COL6A3 | ENST00000491769.1 | n.1340A>C | non_coding_transcript_exon_variant | 9/20 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0183 AC: 2780AN: 152140Hom.: 102 Cov.: 32
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GnomAD3 exomes AF: 0.00539 AC: 1356AN: 251480Hom.: 45 AF XY: 0.00403 AC XY: 548AN XY: 135912
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GnomAD4 exome AF: 0.00229 AC: 3353AN: 1461682Hom.: 95 Cov.: 31 AF XY: 0.00202 AC XY: 1470AN XY: 727148
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GnomAD4 genome ? AF: 0.0184 AC: 2802AN: 152258Hom.: 107 Cov.: 32 AF XY: 0.0175 AC XY: 1304AN XY: 74446
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 01, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 16, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 17, 2012 | - - |
Ullrich congenital muscular dystrophy 1A;CN029274:Bethlem myopathy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 20, 2017 | - - |
Bethlem myopathy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Collagen 6-related myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at