chr21-46124614-G-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.1672-37G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 1,606,578 control chromosomes in the GnomAD database, including 6,032 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 326 hom., cov: 33)

Exomes 𝑓: 0.084 ( 5706 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.364

Publications

4 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=-0.97).

BP6

Variant 21-46124614-G-T is Benign according to our data. Variant chr21-46124614-G-T is described in ClinVar as Benign. ClinVar VariationId is 93917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4 link	c.1672-37G>T	intron_variant	Intron 21 of 27	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3
COL6A2	NM_058174.3 link	c.1672-37G>T	intron_variant	Intron 21 of 27		NP_478054.2	P12110-2
COL6A2	NM_058175.3 link	c.1672-37G>T	intron_variant	Intron 21 of 27		NP_478055.2	P12110-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL6A2	ENST00000300527.9 link	c.1672-37G>T	intron_variant	Intron 21 of 27	1	NM_001849.4	ENSP00000300527.4	P12110-1
COL6A2	ENST00000397763.6 link	c.1672-37G>T	intron_variant	Intron 21 of 27	5		ENSP00000380870.1	P12110-2
COL6A2	ENST00000409416.6 link	c.1672-37G>T	intron_variant	Intron 20 of 26	5		ENSP00000387115.1	P12110-3
COL6A2	ENST00000413758.1 link	c.295-37G>T	intron_variant	Intron 6 of 10	3		ENSP00000395751.1	H7C0M5

Frequencies

GnomAD3 genomes

AF:

0.0578

AC:

8783

AN:

151964

Hom.:

327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0184

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0448

Gnomad ASJ

AF:

0.0784

Gnomad EAS

AF:

0.0195

Gnomad SAS

AF:

0.0624

Gnomad FIN

AF:

0.0271

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.0904

Gnomad OTH

AF:

0.0674

GnomAD2 exomes

AF:

0.0634

AC:

15765

AN:

248770

AF XY:

0.0663

show subpopulations

Gnomad AFR exome

AF:

0.0191

Gnomad AMR exome

AF:

0.0369

Gnomad ASJ exome

AF:

0.0783

Gnomad EAS exome

AF:

0.0234

Gnomad FIN exome

AF:

0.0269

Gnomad NFE exome

AF:

0.0896

Gnomad OTH exome

AF:

0.0684

GnomAD4 exome

AF:

0.0840

AC:

122160

AN:

1454492

Hom.:

5706

Cov.:

AF XY:

0.0835

AC XY:

60474

AN XY:

724016

show subpopulations

African (AFR)

AF:

0.0159

AC:

530

AN:

33340

American (AMR)

AF:

0.0388

AC:

1735

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.0804

AC:

2097

AN:

26070

East Asian (EAS)

AF:

0.0214

AC:

848

AN:

39668

South Asian (SAS)

AF:

0.0627

AC:

5402

AN:

86122

European-Finnish (FIN)

AF:

0.0290

AC:

1518

AN:

52292

Middle Eastern (MID)

AF:

0.115

AC:

656

AN:

5722

European-Non Finnish (NFE)

AF:

0.0946

AC:

104656

AN:

1106510

Other (OTH)

AF:

0.0785

AC:

4718

AN:

60086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

5827

11654

17480

23307

29134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3770

7540

11310

15080

18850

<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:

0.0577

AC:

8779

AN:

152086

Hom.:

326

Cov.:

AF XY:

0.0544

AC XY:

4041

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0184

AC:

762

AN:

41488

American (AMR)

AF:

0.0447

AC:

684

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0784

AC:

272

AN:

3470

East Asian (EAS)

AF:

0.0195

AC:

101

AN:

5168

South Asian (SAS)

AF:

0.0623

AC:

300

AN:

4816

European-Finnish (FIN)

AF:

0.0271

AC:

287

AN:

10610

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0904

AC:

6140

AN:

67928

Other (OTH)

AF:

0.0662

AC:

140

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

403

806

1208

1611

2014

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:

0.0260

Hom.:

Bravo

AF:

0.0579

Asia WGS

AF:

0.0470

AC:

164

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

-0.97

CADD

Benign

0.24

(source)

DANN

Benign

0.70

PhyloP100

-0.36

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