rs149480738
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_001849.4(COL6A2):c.426G>A(p.Thr142=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,612,574 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
COL6A2
NM_001849.4 synonymous
NM_001849.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.57
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 -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 21-46112289-G-A is Benign according to our data. Variant chr21-46112289-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 476488.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
BP7
?
Synonymous conserved (PhyloP=-4.57 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.426G>A | p.Thr142= | synonymous_variant | 3/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.426G>A | p.Thr142= | synonymous_variant | 3/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.426G>A | p.Thr142= | synonymous_variant | 3/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.426G>A | p.Thr142= | synonymous_variant | 3/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.426G>A | p.Thr142= | synonymous_variant | 3/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.426G>A | p.Thr142= | synonymous_variant | 2/27 | 5 | |||
COL6A2 | ENST00000436769.5 | c.426G>A | p.Thr142= | synonymous_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000421 AC: 64AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000130 AC: 32AN: 247018Hom.: 0 AF XY: 0.0000669 AC XY: 9AN XY: 134504
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GnomAD4 exome AF: 0.0000425 AC: 62AN: 1460290Hom.: 0 Cov.: 33 AF XY: 0.0000440 AC XY: 32AN XY: 726456
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GnomAD4 genome ? AF: 0.000420 AC: 64AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74464
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 18, 2016 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 18, 2017 | 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. - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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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