chr21-46116632-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.928-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 1,612,294 control chromosomes in the GnomAD database, including 205,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17064 hom., cov: 32)

Exomes 𝑓: 0.50 ( 188001 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.87

Publications

18 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=-0.86).

BP6

Variant 21-46116632-C-T is Benign according to our data. Variant chr21-46116632-C-T is described in ClinVar as Benign. ClinVar VariationId is 93963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4 link	c.928-19C>T	intron_variant	Intron 8 of 27	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3
COL6A2	NM_058174.3 link	c.928-19C>T	intron_variant	Intron 8 of 27		NP_478054.2	P12110-2
COL6A2	NM_058175.3 link	c.928-19C>T	intron_variant	Intron 8 of 27		NP_478055.2	P12110-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL6A2	ENST00000300527.9 link	c.928-19C>T	intron_variant	Intron 8 of 27	1	NM_001849.4	ENSP00000300527.4	P12110-1
COL6A2	ENST00000397763.6 link	c.928-19C>T	intron_variant	Intron 8 of 27	5		ENSP00000380870.1	P12110-2
COL6A2	ENST00000409416.6 link	c.928-19C>T	intron_variant	Intron 7 of 26	5		ENSP00000387115.1	P12110-3
COL6A2	ENST00000485591.1 link	n.584-19C>T	intron_variant	Intron 4 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.454

AC:

69055

AN:

151958

Hom.:

17046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.582

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.531

Gnomad EAS

AF:

0.440

Gnomad SAS

AF:

0.365

Gnomad FIN

AF:

0.631

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.523

Gnomad OTH

AF:

0.466

GnomAD2 exomes

AF:

0.504

AC:

125989

AN:

249874

AF XY:

0.496

show subpopulations

Gnomad AFR exome

AF:

0.243

Gnomad AMR exome

AF:

0.657

Gnomad ASJ exome

AF:

0.530

Gnomad EAS exome

AF:

0.427

Gnomad FIN exome

AF:

0.638

Gnomad NFE exome

AF:

0.518

Gnomad OTH exome

AF:

0.527

GnomAD4 exome

AF:

0.502

AC:

733123

AN:

1460216

Hom.:

188001

Cov.:

AF XY:

0.498

AC XY:

361697

AN XY:

726432

show subpopulations

African (AFR)

AF:

0.231

AC:

7737

AN:

33468

American (AMR)

AF:

0.648

AC:

28952

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

13880

AN:

26136

East Asian (EAS)

AF:

0.426

AC:

16929

AN:

39696

South Asian (SAS)

AF:

0.364

AC:

31351

AN:

86240

European-Finnish (FIN)

AF:

0.627

AC:

32743

AN:

52204

Middle Eastern (MID)

AF:

0.448

AC:

2578

AN:

5752

European-Non Finnish (NFE)

AF:

0.512

AC:

569479

AN:

1111646

Other (OTH)

AF:

0.488

AC:

29474

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

21363

42727

64090

85454

106817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16292

32584

48876

65168

81460

<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:

0.454

AC:

69088

AN:

152078

Hom.:

17064

Cov.:

AF XY:

0.461

AC XY:

34243

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.252

AC:

10462

AN:

41498

American (AMR)

AF:

0.584

AC:

8927

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

1841

AN:

3470

East Asian (EAS)

AF:

0.440

AC:

2265

AN:

5146

South Asian (SAS)

AF:

0.365

AC:

1757

AN:

4816

European-Finnish (FIN)

AF:

0.631

AC:

6681

AN:

10594

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.523

AC:

35516

AN:

67948

Other (OTH)

AF:

0.461

AC:

974

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1805

3610

5414

7219

9024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.487

Hom.:

10534

Bravo

AF:

0.443

Asia WGS

AF:

0.407

AC:

1417

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 12, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 05, 2016

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. -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Bethlem myopathy 1A

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Myosclerosis

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Ullrich congenital muscular dystrophy 1A

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.26

(source)

DANN

Benign

0.37

PhyloP100

-1.9

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