rs150275851
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_001849.4(COL6A2):c.1816+18del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 1,608,120 control chromosomes in the GnomAD database, including 1,300 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.028 ( 89 hom., cov: 33)
Exomes 𝑓: 0.038 ( 1211 hom. )
Consequence
COL6A2
NM_001849.4 intron
NM_001849.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.12
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 -16 ACMG points.
BP6
Variant 21-46125327-CG-C is Benign according to our data. Variant chr21-46125327-CG-C is described in ClinVar as [Likely_benign]. Clinvar id is 93923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46125327-CG-C is described in Lovd as [Benign]. Variant chr21-46125327-CG-C is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0276 (4200/152268) while in subpopulation NFE AF= 0.0432 (2935/67994). AF 95% confidence interval is 0.0419. There are 89 homozygotes in gnomad4. There are 1973 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 89 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.1816+18del | intron_variant | ENST00000300527.9 | |||
COL6A2 | NM_058174.3 | c.1816+18del | intron_variant | ENST00000397763.6 | |||
COL6A2 | NM_058175.3 | c.1816+18del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.1816+18del | intron_variant | 1 | NM_001849.4 | P1 | |||
COL6A2 | ENST00000397763.6 | c.1816+18del | intron_variant | 5 | NM_058174.3 | ||||
COL6A2 | ENST00000409416.6 | c.1816+18del | intron_variant | 5 | |||||
COL6A2 | ENST00000413758.1 | c.439+18del | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0276 AC: 4202AN: 152150Hom.: 89 Cov.: 33
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GnomAD3 exomes AF: 0.0290 AC: 7126AN: 245630Hom.: 153 AF XY: 0.0295 AC XY: 3929AN XY: 133222
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GnomAD4 exome AF: 0.0376 AC: 54779AN: 1455852Hom.: 1211 Cov.: 36 AF XY: 0.0370 AC XY: 26761AN XY: 723788
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GnomAD4 genome AF: 0.0276 AC: 4200AN: 152268Hom.: 89 Cov.: 33 AF XY: 0.0265 AC XY: 1973AN XY: 74454
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 02, 2012 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 01, 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. - |
Bethlem myopathy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at