dbSNP rs16978875: COL6A2:p.Gln721Gln (chr21-46125978-G-A) – ACMG Classification: Benign (-21 pts)

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.2163G>A(p.Gln721Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00607 in 1,613,066 control chromosomes in the GnomAD database, including 507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 279 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 228 hom. )

Consequence

COL6A2
NM_001849.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.754

Publications

3 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, SD, 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: AR, AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
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=-0.6).

BP6

Variant 21-46125978-G-A is Benign according to our data. Variant chr21-46125978-G-A is described in ClinVar as Benign. ClinVar VariationId is 93935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.754 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001849.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL6A2	NM_001849.4	MANE Select	c.2163G>A	p.Gln721Gln	synonymous	Exon 26 of 28	NP_001840.3
COL6A2	NM_058174.3	MANE Plus Clinical	c.2163G>A	p.Gln721Gln	synonymous	Exon 26 of 28	NP_478054.2	P12110-2
COL6A2	NM_058175.3		c.2163G>A	p.Gln721Gln	synonymous	Exon 26 of 28	NP_478055.2	P12110-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL6A2	ENST00000300527.9	TSL:1 MANE Select	c.2163G>A	p.Gln721Gln	synonymous	Exon 26 of 28	ENSP00000300527.4	P12110-1
COL6A2	ENST00000397763.6	TSL:5 MANE Plus Clinical	c.2163G>A	p.Gln721Gln	synonymous	Exon 26 of 28	ENSP00000380870.1	P12110-2
COL6A2	ENST00000857098.1		c.2358G>A	p.Gln786Gln	synonymous	Exon 26 of 28	ENSP00000527157.1

Frequencies

GnomAD3 genomes

AF:

0.0315

AC:

4798

AN:

152124

Hom.:

279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0301

GnomAD2 exomes

AF:

0.00835

AC:

2097

AN:

251102

AF XY:

0.00622

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.00697

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000617

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00342

AC:

4996

AN:

1460824

Hom.:

228

Cov.:

AF XY:

0.00297

AC XY:

2155

AN XY:

726696

show subpopulations

African (AFR)

AF:

0.112

AC:

3752

AN:

33476

American (AMR)

AF:

0.00823

AC:

368

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000174

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52518

Middle Eastern (MID)

AF:

0.00416

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000347

AC:

386

AN:

1111878

Other (OTH)

AF:

0.00744

AC:

449

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

310

620

930

1240

1550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.0315

AC:

4803

AN:

152242

Hom.:

279

Cov.:

AF XY:

0.0298

AC XY:

2222

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.108

AC:

4490

AN:

41516

American (AMR)

AF:

0.0139

AC:

213

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68024

Other (OTH)

AF:

0.0298

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

203

405

608

810

1013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0171

Hom.:

Bravo

AF:

0.0365

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (3)

Bethlem myopathy 1A (1)

Collagen 6-related myopathy (1)

Myosclerosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.3

(source)

DANN

Benign

0.73

PhyloP100

0.75

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over