rs373369963

Variant names:

Variant summary

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

The NM_001849.4(COL6A2):c.1970-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,610,586 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

Splicing: ADA: 0.0002117

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: -1.08

Publications

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 21-46125775-C-T is Benign according to our data. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836. Variant chr21-46125775-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 288836.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4 link	c.1970-10C>T	intron_variant	Intron 25 of 27	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3
COL6A2	NM_058174.3 link	c.1970-10C>T	intron_variant	Intron 25 of 27		NP_478054.2	P12110-2
COL6A2	NM_058175.3 link	c.1970-10C>T	intron_variant	Intron 25 of 27		NP_478055.2	P12110-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL6A2	ENST00000300527.9 link	c.1970-10C>T	intron_variant	Intron 25 of 27	1	NM_001849.4	ENSP00000300527.4	P12110-1
COL6A2	ENST00000397763.6 link	c.1970-10C>T	intron_variant	Intron 25 of 27	5		ENSP00000380870.1	P12110-2
COL6A2	ENST00000409416.6 link	c.1970-10C>T	intron_variant	Intron 24 of 26	5		ENSP00000387115.1	P12110-3
COL6A2	ENST00000413758.1 link	c.641-10C>T	intron_variant	Intron 10 of 10	3		ENSP00000395751.1	H7C0M5

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000230

AC:

AN:

247356

AF XY:

0.000208

show subpopulations

Gnomad AFR exome

AF:

0.000251

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.000438

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000279

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000256

AC:

374

AN:

1458266

Hom.:

Cov.:

AF XY:

0.000234

AC XY:

170

AN XY:

724968

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33430

American (AMR)

AF:

0.000202

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26106

East Asian (EAS)

AF:

0.000530

AC:

AN:

39624

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86212

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

52080

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000286

AC:

317

AN:

1110122

Other (OTH)

AF:

0.000199

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000355

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41572

American (AMR)

AF:

0.000457

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68032

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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:

0.000382

Hom.:

Bravo

AF:

0.000351

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Sep 11, 2024

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Reported in an individual with pneumonia, neonatal respiratory distress, umbilical hernia, and hypoglycemia, who harbored a second COL6A2 variant in trans, as well as two variants in the DNAH11 gene (PMID: 31965297); In silico analysis indicates that this variant does not alter splicing; This variant is associated with the following publications: (PMID: 31965297) -

Jan 03, 2018

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bethlem myopathy 1A

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Collagen 6-related myopathy

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.51

(source)

DANN

Benign

0.79

PhyloP100

-1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.0020

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