rs115342490

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001849.4(COL6A2):c.-27-89G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 713,700 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 53 hom., cov: 31)

Exomes 𝑓: 0.0024 ( 24 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.77

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:

LOC124905043 (HGNC:):

LOC124905043 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 21-46111361-G-A is Benign according to our data. Variant chr21-46111361-G-A is described in ClinVar as [Benign]. Clinvar id is 679820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0152 (2321/152314) while in subpopulation AFR AF = 0.0499 (2074/41572). AF 95% confidence interval is 0.0481. There are 53 homozygotes in GnomAd4. There are 1113 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 53 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4 link	c.-27-89G>A	intron_variant	Intron 1 of 27	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3
LOC124905043	XR_007067910.1 link	n.671C>T	non_coding_transcript_exon_variant	Exon 1 of 2
COL6A2	NM_058174.3 link	c.-27-89G>A	intron_variant	Intron 1 of 27		NP_478054.2	P12110-2
COL6A2	NM_058175.3 link	c.-27-89G>A	intron_variant	Intron 1 of 27		NP_478055.2	P12110-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL6A2	ENST00000300527.9 link	c.-27-89G>A	intron_variant	Intron 1 of 27	1	NM_001849.4	ENSP00000300527.4	P12110-1
COL6A2	ENST00000397763.6 link	c.-27-89G>A	intron_variant	Intron 1 of 27	5		ENSP00000380870.1	P12110-2
COL6A2	ENST00000436769.5 link	c.-27-89G>A	intron_variant	Intron 1 of 2	2		ENSP00000390418.1	C9JH44
COL6A2	ENST00000409416.6 link	c.-116G>A	upstream_gene_variant		5		ENSP00000387115.1	P12110-3

Frequencies

GnomAD3 genomes

AF:

0.0152

AC:

2318

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0499

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00955

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00868

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0124

GnomAD4 exome

AF:

0.00244

AC:

1369

AN:

561386

Hom.:

AF XY:

0.00208

AC XY:

613

AN XY:

295350

show subpopulations

African (AFR)

AF:

0.0469

AC:

738

AN:

15746

American (AMR)

AF:

0.00426

AC:

130

AN:

30500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17042

East Asian (EAS)

AF:

0.00536

AC:

170

AN:

31726

South Asian (SAS)

AF:

0.000371

AC:

AN:

56574

European-Finnish (FIN)

AF:

0.0000254

AC:

AN:

39328

Middle Eastern (MID)

AF:

0.00381

AC:

AN:

2360

European-Non Finnish (NFE)

AF:

0.000387

AC:

131

AN:

338324

Other (OTH)

AF:

0.00567

AC:

169

AN:

29786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

122

183

244

305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0152

AC:

2321

AN:

152314

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1113

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0499

AC:

2074

AN:

41572

American (AMR)

AF:

0.00954

AC:

146

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00850

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

68028

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

117

233

350

466

583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0145

Hom.:

Bravo

AF:

0.0180

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.44

(source)

DANN

Benign

0.62

PhyloP100

-3.8

PromoterAI

0.0072

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

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rs115342490

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