21-46122464-C-T

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.1573-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0813 in 1,612,192 control chromosomes in the GnomAD database, including 6,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 327 hom., cov: 32)

Exomes 𝑓: 0.084 ( 5722 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.18

Publications

5 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 (BayesDel_noAF=-0.79).

BP6

Variant 21-46122464-C-T is Benign according to our data. Variant chr21-46122464-C-T is described in ClinVar as Benign. ClinVar VariationId is 93912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4 link	c.1573-32C>T	intron_variant	Intron 19 of 27	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3
COL6A2	NM_058174.3 link	c.1573-32C>T	intron_variant	Intron 19 of 27		NP_478054.2	P12110-2
COL6A2	NM_058175.3 link	c.1573-32C>T	intron_variant	Intron 19 of 27		NP_478055.2	P12110-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL6A2	ENST00000300527.9 link	c.1573-32C>T	intron_variant	Intron 19 of 27	1	NM_001849.4	ENSP00000300527.4	P12110-1
COL6A2	ENST00000397763.6 link	c.1573-32C>T	intron_variant	Intron 19 of 27	5		ENSP00000380870.1	P12110-2
COL6A2	ENST00000409416.6 link	c.1573-32C>T	intron_variant	Intron 18 of 26	5		ENSP00000387115.1	P12110-3
COL6A2	ENST00000413758.1 link	c.196-32C>T	intron_variant	Intron 4 of 10	3		ENSP00000395751.1	H7C0M5

Frequencies

GnomAD3 genomes

AF:

0.0575

AC:

8747

AN:

152066

Hom.:

329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.0681

Gnomad AMR

AF:

0.0449

Gnomad ASJ

AF:

0.0783

Gnomad EAS

AF:

0.0195

Gnomad SAS

AF:

0.0628

Gnomad FIN

AF:

0.0265

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0905

Gnomad OTH

AF:

0.0675

GnomAD2 exomes

AF:

0.0630

AC:

15735

AN:

249836

AF XY:

0.0660

show subpopulations

Gnomad AFR exome

AF:

0.0180

Gnomad AMR exome

AF:

0.0366

Gnomad ASJ exome

AF:

0.0781

Gnomad EAS exome

AF:

0.0235

Gnomad FIN exome

AF:

0.0258

Gnomad NFE exome

AF:

0.0895

Gnomad OTH exome

AF:

0.0682

GnomAD4 exome

AF:

0.0838

AC:

122394

AN:

1460008

Hom.:

5722

Cov.:

AF XY:

0.0834

AC XY:

60552

AN XY:

726292

show subpopulations

African (AFR)

AF:

0.0150

AC:

501

AN:

33470

American (AMR)

AF:

0.0386

AC:

1727

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0804

AC:

2101

AN:

26134

East Asian (EAS)

AF:

0.0214

AC:

849

AN:

39698

South Asian (SAS)

AF:

0.0624

AC:

5383

AN:

86244

European-Finnish (FIN)

AF:

0.0279

AC:

1459

AN:

52242

Middle Eastern (MID)

AF:

0.114

AC:

657

AN:

5762

European-Non Finnish (NFE)

AF:

0.0945

AC:

104982

AN:

1111382

Other (OTH)

AF:

0.0784

AC:

4735

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

5839

11679

17518

23358

29197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3784

7568

11352

15136

18920

<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:

0.0574

AC:

8739

AN:

152184

Hom.:

327

Cov.:

AF XY:

0.0540

AC XY:

4015

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0171

AC:

708

AN:

41512

American (AMR)

AF:

0.0448

AC:

686

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0783

AC:

272

AN:

3472

East Asian (EAS)

AF:

0.0196

AC:

101

AN:

5166

South Asian (SAS)

AF:

0.0627

AC:

302

AN:

4820

European-Finnish (FIN)

AF:

0.0265

AC:

281

AN:

10610

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0905

AC:

6156

AN:

67992

Other (OTH)

AF:

0.0664

AC:

140

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

403

806

1209

1612

2015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0738

Hom.:

108

Bravo

AF:

0.0576

Asia WGS

AF:

0.0460

AC:

162

AN:

3478

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.8

(source)

DANN

Benign

0.73

PhyloP100

1.2

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