Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The ENST00000300527.9(COL6A2):c.510C>T(p.Cys170Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,606,742 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 24 hom. )

Consequence

COL6A2
ENST00000300527.9 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.782

Publications

3 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: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 21-46112373-C-T is Benign according to our data. Variant chr21-46112373-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 196330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.782 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 24 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000300527.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COL6A2	NM_001849.4	MANE Select	c.510C>T	p.Cys170Cys	synonymous	Exon 3 of 28	NP_001840.3
COL6A2	NM_058174.3	MANE Plus Clinical	c.510C>T	p.Cys170Cys	synonymous	Exon 3 of 28	NP_478054.2
COL6A2	NM_058175.3		c.510C>T	p.Cys170Cys	synonymous	Exon 3 of 28	NP_478055.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COL6A2	ENST00000300527.9	TSL:1 MANE Select	c.510C>T	p.Cys170Cys	synonymous	Exon 3 of 28	ENSP00000300527.4
COL6A2	ENST00000397763.6	TSL:5 MANE Plus Clinical	c.510C>T	p.Cys170Cys	synonymous	Exon 3 of 28	ENSP00000380870.1
COL6A2	ENST00000409416.6	TSL:5	c.510C>T	p.Cys170Cys	synonymous	Exon 2 of 27	ENSP00000387115.1

Frequencies

GnomAD3 genomes

AF:

0.00336

AC:

510

AN:

151710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.00348

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00233

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00493

Gnomad OTH

AF:

0.00527

GnomAD2 exomes

AF:

0.00342

AC:

796

AN:

233060

AF XY:

0.00359

show subpopulations

Gnomad AFR exome

AF:

0.00139

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00171

Gnomad NFE exome

AF:

0.00549

Gnomad OTH exome

AF:

0.00400

GnomAD4 exome

AF:

0.00514

AC:

7481

AN:

1454910

Hom.:

Cov.:

AF XY:

0.00515

AC XY:

3729

AN XY:

723656

show subpopulations

African (AFR)

AF:

0.000900

AC:

AN:

33344

American (AMR)

AF:

0.00234

AC:

104

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.000154

AC:

AN:

25962

East Asian (EAS)

AF:

0.00

AC:

AN:

39536

South Asian (SAS)

AF:

0.00259

AC:

223

AN:

86038

European-Finnish (FIN)

AF:

0.00211

AC:

105

AN:

49860

Middle Eastern (MID)

AF:

0.00400

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00608

AC:

6744

AN:

1109866

Other (OTH)

AF:

0.00413

AC:

248

AN:

60034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

518

1036

1554

2072

2590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.00335

AC:

509

AN:

151832

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

236

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.00133

AC:

AN:

41454

American (AMR)

AF:

0.00347

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5088

South Asian (SAS)

AF:

0.00233

AC:

AN:

4724

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00493

AC:

335

AN:

67926

Other (OTH)

AF:

0.00521

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

112

140

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:

0.00447

Hom.:

Bravo

AF:

0.00348

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00605

EpiControl

AF:

0.00529

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (2)

Bethlem myopathy 1A (1)

Collagen 6-related myopathy (1)

Inborn genetic diseases (1)

Myosclerosis (1)

Ullrich congenital muscular dystrophy 1A;C1850671:Myosclerosis;CN029274:Bethlem myopathy 1A (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.1

(source)

DANN

Benign

0.79

PhyloP100

-0.78

Mutation Taster

=99/1

polymorphism

(source)

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.

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