rs2276101

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001849.4(COL6A2):c.1817-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,611,024 control chromosomes in the GnomAD database, including 5,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 616 hom., cov: 33)

Exomes 𝑓: 0.050 ( 5043 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.74

Publications

6 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004430741).

BP6

Variant 21-46125432-C-T is Benign according to our data. Variant chr21-46125432-C-T is described in ClinVar as [Benign]. Clinvar id is 93924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4 link	c.1817-33C>T	intron_variant	Intron 24 of 27	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3
COL6A2	NM_058174.3 link	c.1817-33C>T	intron_variant	Intron 24 of 27		NP_478054.2	P12110-2
COL6A2	NM_058175.3 link	c.1817-33C>T	intron_variant	Intron 24 of 27		NP_478055.2	P12110-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL6A2	ENST00000300527.9 link	c.1817-33C>T		intron_variant	Intron 24 of 27	1	NM_001849.4	ENSP00000300527.4	P12110-1
COL6A2	ENST00000413758.1 link	c.455C>T	p.Pro152Leu	missense_variant	Exon 10 of 11	3		ENSP00000395751.1	H7C0M5
COL6A2	ENST00000397763.6 link	c.1817-33C>T		intron_variant	Intron 24 of 27	5		ENSP00000380870.1	P12110-2
COL6A2	ENST00000409416.6 link	c.1817-33C>T		intron_variant	Intron 23 of 26	5		ENSP00000387115.1	P12110-3

Frequencies

GnomAD3 genomes

AF:

0.0663

AC:

10059

AN:

151834

Hom.:

614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0858

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0760

Gnomad ASJ

AF:

0.0401

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.0925

Gnomad FIN

AF:

0.0252

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0361

Gnomad OTH

AF:

0.0824

GnomAD2 exomes

AF:

0.0753

AC:

18789

AN:

249494

AF XY:

0.0724

show subpopulations

Gnomad AFR exome

AF:

0.0908

Gnomad AMR exome

AF:

0.0896

Gnomad ASJ exome

AF:

0.0347

Gnomad EAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.0257

Gnomad NFE exome

AF:

0.0379

Gnomad OTH exome

AF:

0.0577

GnomAD4 exome

AF:

0.0505

AC:

73631

AN:

1459070

Hom.:

5043

Cov.:

AF XY:

0.0512

AC XY:

37190

AN XY:

725804

show subpopulations

African (AFR)

AF:

0.0864

AC:

2888

AN:

33438

American (AMR)

AF:

0.0894

AC:

3994

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0368

AC:

961

AN:

26090

East Asian (EAS)

AF:

0.408

AC:

16200

AN:

39668

South Asian (SAS)

AF:

0.0788

AC:

6792

AN:

86188

European-Finnish (FIN)

AF:

0.0253

AC:

1317

AN:

52150

Middle Eastern (MID)

AF:

0.0732

AC:

422

AN:

5766

European-Non Finnish (NFE)

AF:

0.0338

AC:

37491

AN:

1110782

Other (OTH)

AF:

0.0591

AC:

3566

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

3272

6543

9815

13086

16358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1590

3180

4770

6360

7950

<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:

0.0662

AC:

10063

AN:

151954

Hom.:

616

Cov.:

AF XY:

0.0682

AC XY:

5066

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0856

AC:

3553

AN:

41514

American (AMR)

AF:

0.0759

AC:

1160

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0401

AC:

139

AN:

3466

East Asian (EAS)

AF:

0.348

AC:

1788

AN:

5142

South Asian (SAS)

AF:

0.0924

AC:

445

AN:

4818

European-Finnish (FIN)

AF:

0.0252

AC:

267

AN:

10614

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0361

AC:

2447

AN:

67798

Other (OTH)

AF:

0.0839

AC:

177

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

441

881

1322

1762

2203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0453

Hom.:

Bravo

AF:

0.0731

TwinsUK

AF:

0.0326

AC:

121

ALSPAC

AF:

0.0374

AC:

144

ESP6500AA

AF:

0.0867

AC:

382

ESP6500EA

AF:

0.0388

AC:

334

ExAC

AF:

0.0751

AC:

9111

Asia WGS

AF:

0.169

AC:

587

AN:

3478

EpiCase

AF:

0.0412

EpiControl

AF:

0.0389

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 16, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jun 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.057

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.030

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0044

MetaSVM

Benign

-1.0

PhyloP100

-3.7

PROVEAN

Benign

-1.2

REVEL

Benign

0.096

Sift

Benign

0.13

Sift4G

Benign

0.13

ClinPred

0.0069

GERP RS

-3.5

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over