rs2839114
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001849.4(COL6A2):c.2184G>A(p.Val728=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,612,720 control chromosomes in the GnomAD database, including 112,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.33 ( 9456 hom., cov: 32)
Exomes 𝑓: 0.37 ( 103082 hom. )
Consequence
COL6A2
NM_001849.4 synonymous
NM_001849.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.86
Genes affected
COL6A2 (HGNC:2212): (collagen type VI alpha 2 chain) This gene encodes one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The product of this gene contains several domains similar to von Willebrand Factor type A domains. 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 this gene are associated with Bethlem myopathy and Ullrich scleroatonic muscular dystrophy. Three transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 21-46125999-G-A is Benign according to our data. Variant chr21-46125999-G-A is described in ClinVar as [Benign]. Clinvar id is 93936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46125999-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.86 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.2184G>A | p.Val728= | synonymous_variant | 26/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.2184G>A | p.Val728= | synonymous_variant | 26/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.2184G>A | p.Val728= | synonymous_variant | 26/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.2184G>A | p.Val728= | synonymous_variant | 26/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.2184G>A | p.Val728= | synonymous_variant | 26/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.2184G>A | p.Val728= | synonymous_variant | 25/27 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.329 AC: 49959AN: 151914Hom.: 9442 Cov.: 32
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GnomAD3 exomes AF: 0.389 AC: 97680AN: 250960Hom.: 20865 AF XY: 0.380 AC XY: 51596AN XY: 135766
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GnomAD4 exome AF: 0.369 AC: 539562AN: 1460686Hom.: 103082 Cov.: 75 AF XY: 0.367 AC XY: 266375AN XY: 726608
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GnomAD4 genome ? AF: 0.329 AC: 49979AN: 152034Hom.: 9456 Cov.: 32 AF XY: 0.335 AC XY: 24906AN XY: 74300
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ClinVar
Significance: Benign
Submissions summary: Benign:13
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 16, 2017 | 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, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 28, 2018 | - - |
Myosclerosis Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Bethlem myopathy 1A Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Collagen 6-related myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Ullrich congenital muscular dystrophy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 13, 2017 | - - |
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