chr21-46125432-C-T
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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.1817-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,611,024 control chromosomes in the GnomAD database, including 5,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.066 ( 616 hom., cov: 33)
Exomes 𝑓: 0.050 ( 5043 hom. )
Consequence
COL6A2
NM_001849.4 intron
NM_001849.4 intron
Scores
15
Clinical Significance
Conservation
PhyloP100: -3.74
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 (MetaRNN=0.004430741).
BP6
Variant 21-46125432-C-T is Benign according to our data. Variant chr21-46125432-C-T is described in ClinVar as [Benign]. Clinvar id is 93924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46125432-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.1817-33C>T | intron_variant | ENST00000300527.9 | |||
COL6A2 | NM_058174.3 | c.1817-33C>T | intron_variant | ENST00000397763.6 | |||
COL6A2 | NM_058175.3 | c.1817-33C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.1817-33C>T | intron_variant | 1 | NM_001849.4 | P1 | |||
COL6A2 | ENST00000397763.6 | c.1817-33C>T | intron_variant | 5 | NM_058174.3 | ||||
COL6A2 | ENST00000413758.1 | c.455C>T | p.Pro152Leu | missense_variant | 10/11 | 3 | |||
COL6A2 | ENST00000409416.6 | c.1817-33C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0663 AC: 10059AN: 151834Hom.: 614 Cov.: 33
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GnomAD3 exomes AF: 0.0753 AC: 18789AN: 249494Hom.: 1583 AF XY: 0.0724 AC XY: 9797AN XY: 135312
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GnomAD4 exome AF: 0.0505 AC: 73631AN: 1459070Hom.: 5043 Cov.: 37 AF XY: 0.0512 AC XY: 37190AN XY: 725804
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GnomAD4 genome AF: 0.0662 AC: 10063AN: 151954Hom.: 616 Cov.: 33 AF XY: 0.0682 AC XY: 5066AN XY: 74304
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ClinVar
Significance: Benign
Submissions summary: Benign:4
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:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 16, 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. - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P;P;P
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
ClinPred
T
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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