rs1077182
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001849.4(COL6A2):c.1521+21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,611,126 control chromosomes in the GnomAD database, including 24,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.12 ( 1376 hom., cov: 33)
Exomes 𝑓: 0.17 ( 22931 hom. )
Consequence
COL6A2
NM_001849.4 intron
NM_001849.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.648
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 21-46121639-A-G is Benign according to our data. Variant chr21-46121639-A-G is described in ClinVar as [Benign]. Clinvar id is 93908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46121639-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.1521+21A>G | intron_variant | ENST00000300527.9 | |||
COL6A2 | NM_058174.3 | c.1521+21A>G | intron_variant | ENST00000397763.6 | |||
COL6A2 | NM_058175.3 | c.1521+21A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.1521+21A>G | intron_variant | 1 | NM_001849.4 | P1 | |||
COL6A2 | ENST00000397763.6 | c.1521+21A>G | intron_variant | 5 | NM_058174.3 | ||||
COL6A2 | ENST00000409416.6 | c.1521+21A>G | intron_variant | 5 | |||||
COL6A2 | ENST00000413758.1 | c.144+21A>G | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.118 AC: 17937AN: 152088Hom.: 1377 Cov.: 33
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GnomAD3 exomes AF: 0.120 AC: 29797AN: 247474Hom.: 2231 AF XY: 0.124 AC XY: 16678AN XY: 134562
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GnomAD4 exome AF: 0.168 AC: 244629AN: 1458920Hom.: 22931 Cov.: 33 AF XY: 0.165 AC XY: 119876AN XY: 725834
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GnomAD4 genome ? AF: 0.118 AC: 17941AN: 152206Hom.: 1376 Cov.: 33 AF XY: 0.111 AC XY: 8269AN XY: 74396
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 16, 2012 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2018 | 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. - |
Computational scores
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BayesDel_noAF
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CADD
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DANN
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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