NM_001849.4:c.1095G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_001849.4(COL6A2):c.1095G>A(p.Glu365Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,612,866 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 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

COL6A2
NM_001849.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.691

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 21-46117915-G-A is Benign according to our data. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272. Variant chr21-46117915-G-A is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 286272.

BP7

Synonymous conserved (PhyloP=0.691 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4 link	c.1095G>A	p.Glu365Glu	synonymous_variant	Exon 12 of 28	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3
COL6A2	NM_058174.3 link	c.1095G>A	p.Glu365Glu	synonymous_variant	Exon 12 of 28		NP_478054.2	P12110-2
COL6A2	NM_058175.3 link	c.1095G>A	p.Glu365Glu	synonymous_variant	Exon 12 of 28		NP_478055.2	P12110-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL6A2	ENST00000300527.9 link	c.1095G>A	p.Glu365Glu	synonymous_variant	Exon 12 of 28	1	NM_001849.4	ENSP00000300527.4	P12110-1
COL6A2	ENST00000397763.6 link	c.1095G>A	p.Glu365Glu	synonymous_variant	Exon 12 of 28	5		ENSP00000380870.1	P12110-2
COL6A2	ENST00000409416.6 link	c.1095G>A	p.Glu365Glu	synonymous_variant	Exon 11 of 27	5		ENSP00000387115.1	P12110-3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000363

AC:

AN:

248166

AF XY:

0.0000371

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000357

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000424

AC:

AN:

1460700

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

726632

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.000112

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52662

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000486

AC:

AN:

1111830

Other (OTH)

AF:

0.0000497

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000282

Hom.:

Bravo

AF:

0.0000151

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Feb 16, 2016

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bethlem myopathy 1A

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.55

CADD

Benign

7.3

(source)

DANN

Benign

0.33

PhyloP100

0.69

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