Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001849.4(COL6A2):c.*5G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000485 in 1,588,418 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 0.00024 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

COL6A2
NM_001849.4 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: -1.18

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

COL6A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 21-46132557-G-A is Benign according to our data. Variant chr21-46132557-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 284976.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001849.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A2	NM_001849.4	MANE Select	c.*5G>A		3_prime_UTR	Exon 28 of 28	NP_001840.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A2	ENST00000300527.9	TSL:1 MANE Select	c.*5G>A		3_prime_UTR	Exon 28 of 28	ENSP00000300527.4

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000795

AC:

AN:

201226

AF XY:

0.0000630

show subpopulations

Gnomad AFR exome

AF:

0.000818

Gnomad AMR exome

AF:

0.0000317

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000190

Gnomad FIN exome

AF:

0.0000837

Gnomad NFE exome

AF:

0.0000114

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000286

AC:

AN:

1436070

Hom.:

Cov.:

AF XY:

0.0000266

AC XY:

AN XY:

713746

show subpopulations

African (AFR)

AF:

0.000513

AC:

AN:

33128

American (AMR)

AF:

0.0000234

AC:

AN:

42776

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25798

East Asian (EAS)

AF:

0.0000772

AC:

AN:

38854

South Asian (SAS)

AF:

0.0000356

AC:

AN:

84256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41372

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.0000109

AC:

AN:

1104510

Other (OTH)

AF:

0.0000671

AC:

AN:

59630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

AF:

0.000236

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000649

AC:

AN:

41582

American (AMR)

AF:

0.000261

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68028

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000133

Hom.:

Bravo

AF:

0.000242

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bethlem myopathy 1A (2)

Collagen 6-related myopathy (1)

Myosclerosis (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.23

(source)

DANN

Benign

0.91

PhyloP100

-1.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs377195134

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over