GeneBe

rs138363207

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001849.4(COL6A2):​c.2423-22_2423-18delCGGCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,310 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.874

Publications

0 publications found
Variant links:
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]
COL6A2 Gene-Disease associations (from GenCC):
  • collagen 6-related myopathy
    Inheritance: AD, AR Classification: DEFINITIVE Submitted by: ClinGen
  • Ullrich congenital muscular dystrophy 1B
    Inheritance: AR, AD Classification: DEFINITIVE Submitted by: G2P
  • Bethlem myopathy 1A
    Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp
  • Ullrich congenital muscular dystrophy 1A
    Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
  • Bethlem myopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Ullrich congenital muscular dystrophy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • myosclerosis
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL6A2NM_001849.4 linkc.2423-22_2423-18delCGGCC intron_variant Intron 26 of 27 ENST00000300527.9 NP_001840.3 P12110-1A0A384MDP3
COL6A2NM_058174.3 linkc.2423-22_2423-18delCGGCC intron_variant Intron 26 of 27 NP_478054.2 P12110-2
COL6A2NM_058175.3 linkc.2423-22_2423-18delCGGCC intron_variant Intron 26 of 27 NP_478055.2 P12110-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL6A2ENST00000300527.9 linkc.2423-26_2423-22delGGCCC intron_variant Intron 26 of 27 1 NM_001849.4 ENSP00000300527.4 P12110-1
COL6A2ENST00000397763.6 linkc.2423-26_2423-22delGGCCC intron_variant Intron 26 of 27 5 ENSP00000380870.1 P12110-2
COL6A2ENST00000409416.6 linkc.2423-26_2423-22delGGCCC intron_variant Intron 25 of 26 5 ENSP00000387115.1 P12110-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459310
Hom.:
0
AF XY:
0.00000138
AC XY:
1
AN XY:
726084
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33476
American (AMR)
AF:
0.00
AC:
0
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26126
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86216
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52820
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
9.01e-7
AC:
1
AN:
1110172
Other (OTH)
AF:
0.00
AC:
0
AN:
60334
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs138363207; hg19: chr21-47546390; API