chr21-46111342-G-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001849.4(COL6A2):c.-27-108G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 650,608 control chromosomes in the GnomAD database, including 194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.017 ( 43 hom., cov: 31)
Exomes 𝑓: 0.020 ( 151 hom. )
Consequence
COL6A2
NM_001849.4 intron
NM_001849.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.684
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 21-46111342-G-C is Benign according to our data. Variant chr21-46111342-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 677612.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0167 (2538/152344) while in subpopulation NFE AF= 0.0294 (1998/68024). AF 95% confidence interval is 0.0283. There are 43 homozygotes in gnomad4. There are 1112 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 43 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.-27-108G>C | intron_variant | ENST00000300527.9 | |||
COL6A2 | NM_058174.3 | c.-27-108G>C | intron_variant | ENST00000397763.6 | |||
LOC124905043 | XR_007067910.1 | n.690C>G | non_coding_transcript_exon_variant | 1/2 | |||
COL6A2 | NM_058175.3 | c.-27-108G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.-27-108G>C | intron_variant | 1 | NM_001849.4 | P1 | |||
COL6A2 | ENST00000397763.6 | c.-27-108G>C | intron_variant | 5 | NM_058174.3 | ||||
COL6A2 | ENST00000436769.5 | c.-27-108G>C | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0167 AC: 2538AN: 152226Hom.: 43 Cov.: 31
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GnomAD4 exome AF: 0.0204 AC: 10147AN: 498264Hom.: 151 AF XY: 0.0199 AC XY: 5230AN XY: 262626
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely 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. - |
Computational scores
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Benign
Cadd
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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