NM_001849.4:c.2697G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001849.4(COL6A2):c.2697G>T(p.Thr899Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 1,575,690 control chromosomes in the GnomAD database, including 1,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T899T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.028 ( 89 hom., cov: 34)

Exomes 𝑓: 0.042 ( 1408 hom. )

Consequence

COL6A2
NM_001849.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -4.97

Publications

11 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 21-46132189-G-T is Benign according to our data. Variant chr21-46132189-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 93944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.97 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4 link	c.2697G>T	p.Thr899Thr	synonymous_variant	Exon 28 of 28	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9 link	c.2697G>T	p.Thr899Thr	synonymous_variant	Exon 28 of 28	1	NM_001849.4	ENSP00000300527.4		P12110-1

Frequencies

GnomAD3 genomes

AF:

0.0282

AC:

4292

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00755

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.0306

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0447

Gnomad FIN

AF:

0.0263

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0427

Gnomad OTH

AF:

0.0205

GnomAD2 exomes

AF:

0.0342

AC:

6339

AN:

185290

AF XY:

0.0367

show subpopulations

Gnomad AFR exome

AF:

0.00635

Gnomad AMR exome

AF:

0.0230

Gnomad ASJ exome

AF:

0.0316

Gnomad EAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.0268

Gnomad NFE exome

AF:

0.0429

Gnomad OTH exome

AF:

0.0360

GnomAD4 exome

AF:

0.0421

AC:

59891

AN:

1423390

Hom.:

1408

Cov.:

AF XY:

0.0424

AC XY:

29916

AN XY:

705294

show subpopulations

African (AFR)

AF:

0.00657

AC:

213

AN:

32418

American (AMR)

AF:

0.0233

AC:

909

AN:

39016

Ashkenazi Jewish (ASJ)

AF:

0.0311

AC:

792

AN:

25474

East Asian (EAS)

AF:

0.0000539

AC:

AN:

37080

South Asian (SAS)

AF:

0.0548

AC:

4512

AN:

82284

European-Finnish (FIN)

AF:

0.0276

AC:

1337

AN:

48530

Middle Eastern (MID)

AF:

0.0306

AC:

175

AN:

5726

European-Non Finnish (NFE)

AF:

0.0455

AC:

49754

AN:

1093890

Other (OTH)

AF:

0.0373

AC:

2197

AN:

58972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

4310

8620

12931

17241

21551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1936

3872

5808

7744

9680

<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:

0.0281

AC:

4287

AN:

152300

Hom.:

Cov.:

AF XY:

0.0275

AC XY:

2046

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00753

AC:

313

AN:

41574

American (AMR)

AF:

0.0265

AC:

406

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0306

AC:

106

AN:

3468

East Asian (EAS)

AF:

0.00135

AC:

AN:

5186

South Asian (SAS)

AF:

0.0446

AC:

215

AN:

4826

European-Finnish (FIN)

AF:

0.0263

AC:

279

AN:

10614

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0427

AC:

2903

AN:

68008

Other (OTH)

AF:

0.0203

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

221

442

664

885

1106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0170

Hom.:

Bravo

AF:

0.0266

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 16, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 12, 2023

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Myosclerosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glutamate formiminotransferase deficiency

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bethlem myopathy 1A

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Collagen 6-related myopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely 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

-0.90

CADD

Benign

0.094

(source)

DANN

Benign

0.88

PhyloP100

-5.0

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over