21-46111488-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP7
The NM_001849.4(COL6A2):c.12C>T(p.Gly4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,611,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
COL6A2
NM_001849.4 synonymous
NM_001849.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.419
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 -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP7
Synonymous conserved (PhyloP=-0.419 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.12C>T | p.Gly4= | synonymous_variant | 2/28 | ENST00000300527.9 | NP_001840.3 | |
COL6A2 | NM_058174.3 | c.12C>T | p.Gly4= | synonymous_variant | 2/28 | ENST00000397763.6 | NP_478054.2 | |
LOC124905043 | XR_007067910.1 | n.544G>A | non_coding_transcript_exon_variant | 1/2 | ||||
COL6A2 | NM_058175.3 | c.12C>T | p.Gly4= | synonymous_variant | 2/28 | NP_478055.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.12C>T | p.Gly4= | synonymous_variant | 2/28 | 1 | NM_001849.4 | ENSP00000300527 | P1 | |
COL6A2 | ENST00000397763.6 | c.12C>T | p.Gly4= | synonymous_variant | 2/28 | 5 | NM_058174.3 | ENSP00000380870 | ||
COL6A2 | ENST00000409416.6 | c.12C>T | p.Gly4= | synonymous_variant | 1/27 | 5 | ENSP00000387115 | |||
COL6A2 | ENST00000436769.5 | c.12C>T | p.Gly4= | synonymous_variant | 2/3 | 2 | ENSP00000390418 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 30
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459662Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 725990
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74350
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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 | Labcorp Genetics (formerly Invitae), Labcorp | Aug 03, 2021 | 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 has not been reported in the literature in individuals affected with COL6A2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects codon 4 of the COL6A2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the COL6A2 protein. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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