rs199513044

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001849.4(COL6A2):c.1333-10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000653 in 1,521,440 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00099 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00062 ( 1 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

Splicing: ADA: 0.01282

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:8

Conservation

PhyloP100: 0.147

Publications

1 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 21-46120505-C-G is Benign according to our data. Variant chr21-46120505-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 194622.

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	Effect	Exon Rank	Protein	UniProt
COL6A2	NM_001849.4	MANE Select	c.1333-10C>G	intron	N/A	NP_001840.3
COL6A2	NM_058174.3	MANE Plus Clinical	c.1333-10C>G	intron	N/A	NP_478054.2	P12110-2
COL6A2	NM_058175.3		c.1333-10C>G	intron	N/A	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.1333-10C>G		intron	N/A	ENSP00000300527.4	P12110-1
COL6A2	ENST00000397763.6	TSL:5 MANE Plus Clinical	c.1333-10C>G		intron	N/A	ENSP00000380870.1	P12110-2
COL6A2	ENST00000857098.1		c.1518C>G	p.Pro506Pro	synonymous	Exon 16 of 28	ENSP00000527157.1

Frequencies

GnomAD3 genomes

AF:

0.000992

AC:

151

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000918

AC:

111

AN:

120944

AF XY:

0.000756

show subpopulations

Gnomad AFR exome

AF:

0.000142

Gnomad AMR exome

AF:

0.000226

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00261

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.00123

GnomAD4 exome

AF:

0.000616

AC:

843

AN:

1369128

Hom.:

Cov.:

AF XY:

0.000633

AC XY:

427

AN XY:

674984

show subpopulations

African (AFR)

AF:

0.0000335

AC:

AN:

29884

American (AMR)

AF:

0.000103

AC:

AN:

28988

Ashkenazi Jewish (ASJ)

AF:

0.00237

AC:

AN:

23244

East Asian (EAS)

AF:

0.00

AC:

AN:

34970

South Asian (SAS)

AF:

0.0000794

AC:

AN:

75528

European-Finnish (FIN)

AF:

0.00239

AC:

113

AN:

47236

Middle Eastern (MID)

AF:

0.000205

AC:

AN:

4888

European-Non Finnish (NFE)

AF:

0.000598

AC:

639

AN:

1067942

Other (OTH)

AF:

0.000443

AC:

AN:

56448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

118

158

197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000991

AC:

151

AN:

152312

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41574

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00273

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00160

AC:

109

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00230

Hom.:

Bravo

AF:

0.000536

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Bethlem myopathy 1A (1)

COL6A2-related disorder (1)

Collagen 6-related myopathy (1)

Myosclerosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.15

PromoterAI

0.051

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.013

dbscSNV1_RF

Benign

0.046

SpliceAI score (max)

0.010

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