chr21-46126198-GAGA-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM4_Supporting
The NM_001849.4(COL6A2):c.2386_2388del(p.Lys796del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,451,094 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
COL6A2
NM_001849.4 inframe_deletion
NM_001849.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.08
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 Uncertain_significance. Variant got 1 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_001849.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.2386_2388del | p.Lys796del | inframe_deletion | 26/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.2386_2388del | p.Lys796del | inframe_deletion | 26/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.2386_2388del | p.Lys796del | inframe_deletion | 26/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.2386_2388del | p.Lys796del | inframe_deletion | 26/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.2386_2388del | p.Lys796del | inframe_deletion | 26/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.2386_2388del | p.Lys796del | inframe_deletion | 25/27 | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.0000165 AC: 4AN: 242878Hom.: 0 AF XY: 0.0000227 AC XY: 3AN XY: 132108
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GnomAD4 exome AF: 0.0000117 AC: 17AN: 1451094Hom.: 0 AF XY: 0.0000166 AC XY: 12AN XY: 722188
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GnomAD4 genome Cov.: 33
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | ClinVar contains an entry for this variant (Variation ID: 542970). This variant has not been reported in the literature in individuals affected with COL6A2-related conditions. This variant is present in population databases (rs747378168, gnomAD 0.01%). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant, c.2386_2388del, results in the deletion of 1 amino acid(s) of the COL6A2 protein (p.Lys796del), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -37
Find out detailed SpliceAI scores and Pangolin per-transcript scores at