chr21-46120530-G-C
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_001849.4(COL6A2):āc.1348G>Cā(p.Glu450Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000143 in 1,491,650 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 34)
Exomes š: 0.00015 ( 0 hom. )
Consequence
COL6A2
NM_001849.4 missense
NM_001849.4 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 3.92
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 Likely_benign. Variant got -1 ACMG points.
BP6
Variant 21-46120530-G-C is Benign according to our data. Variant chr21-46120530-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 288611.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.1348G>C | p.Glu450Gln | missense_variant | 16/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.1348G>C | p.Glu450Gln | missense_variant | 16/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.1348G>C | p.Glu450Gln | missense_variant | 16/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.1348G>C | p.Glu450Gln | missense_variant | 16/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.1348G>C | p.Glu450Gln | missense_variant | 16/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.1348G>C | p.Glu450Gln | missense_variant | 15/27 | 5 | |||
COL6A2 | ENST00000413758.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152160Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000732 AC: 7AN: 95582Hom.: 0 AF XY: 0.0000599 AC XY: 3AN XY: 50118
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GnomAD4 exome AF: 0.000154 AC: 206AN: 1339490Hom.: 0 Cov.: 32 AF XY: 0.000150 AC XY: 99AN XY: 657874
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152160Hom.: 0 Cov.: 34 AF XY: 0.0000404 AC XY: 3AN XY: 74330
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 07, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 14, 2020 | - - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;N;N;N
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
D;D;D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
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