rs113002150
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_001849.4(COL6A2):c.2517C>T(p.Asp839=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000416 in 1,609,770 control chromosomes in the GnomAD database, including 3 homozygotes. 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 0.00027 ( 1 hom., cov: 34)
Exomes 𝑓: 0.00043 ( 2 hom. )
Consequence
COL6A2
NM_001849.4 synonymous
NM_001849.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.07
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
Variant 21-46132009-C-T is Benign according to our data. Variant chr21-46132009-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 196113.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=4, Benign=1}. Variant chr21-46132009-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.07 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.2517C>T | p.Asp839= | synonymous_variant | 28/28 | ENST00000300527.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.2517C>T | p.Asp839= | synonymous_variant | 28/28 | 1 | NM_001849.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000269 AC: 41AN: 152210Hom.: 1 Cov.: 34
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GnomAD3 exomes AF: 0.000363 AC: 87AN: 239484Hom.: 0 AF XY: 0.000388 AC XY: 51AN XY: 131398
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GnomAD4 exome AF: 0.000432 AC: 629AN: 1457560Hom.: 2 Cov.: 33 AF XY: 0.000462 AC XY: 335AN XY: 725298
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GnomAD4 genome ? AF: 0.000269 AC: 41AN: 152210Hom.: 1 Cov.: 34 AF XY: 0.000269 AC XY: 20AN XY: 74358
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 03, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 25, 2019 | - - |
Myosclerosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
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. - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
COL6A2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 27, 2019 | 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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at