rs7279347

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001849.4(COL6A2):c.1116+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,598,598 control chromosomes in the GnomAD database, including 212,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19021 hom., cov: 32)

Exomes 𝑓: 0.51 ( 193518 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.08

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 21-46117968-G-A is Benign according to our data. Variant chr21-46117968-G-A is described in ClinVar as [Benign]. Clinvar id is 93900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46117968-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4 link	c.1116+32G>A	intron_variant	Intron 12 of 27	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3
COL6A2	NM_058174.3 link	c.1116+32G>A	intron_variant	Intron 12 of 27		NP_478054.2	P12110-2
COL6A2	NM_058175.3 link	c.1116+32G>A	intron_variant	Intron 12 of 27		NP_478055.2	P12110-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL6A2	ENST00000300527.9 link	c.1116+32G>A	intron_variant	Intron 12 of 27	1	NM_001849.4	ENSP00000300527.4	P12110-1
COL6A2	ENST00000397763.6 link	c.1116+32G>A	intron_variant	Intron 12 of 27	5		ENSP00000380870.1	P12110-2
COL6A2	ENST00000409416.6 link	c.1116+32G>A	intron_variant	Intron 11 of 26	5		ENSP00000387115.1	P12110-3

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74683

AN:

151796

Hom.:

18990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.583

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.533

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.638

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.527

Gnomad OTH

AF:

0.495

GnomAD3 exomes

AF:

0.529

AC:

124315

AN:

235112

Hom.:

33538

AF XY:

0.522

AC XY:

66552

AN XY:

127376

show subpopulations

Gnomad AFR exome

AF:

0.361

Gnomad AMR exome

AF:

0.668

Gnomad ASJ exome

AF:

0.537

Gnomad EAS exome

AF:

0.419

Gnomad SAS exome

AF:

0.448

Gnomad FIN exome

AF:

0.649

Gnomad NFE exome

AF:

0.525

Gnomad OTH exome

AF:

0.546

GnomAD4 exome

AF:

0.514

AC:

744013

AN:

1446682

Hom.:

193518

Cov.:

AF XY:

0.512

AC XY:

367594

AN XY:

717682

show subpopulations

Gnomad4 AFR exome

AF:

0.352

Gnomad4 AMR exome

AF:

0.658

Gnomad4 ASJ exome

AF:

0.534

Gnomad4 EAS exome

AF:

0.413

Gnomad4 SAS exome

AF:

0.447

Gnomad4 FIN exome

AF:

0.634

Gnomad4 NFE exome

AF:

0.517

Gnomad4 OTH exome

AF:

0.505

GnomAD4 genome

AF:

0.492

AC:

74750

AN:

151916

Hom.:

19021

Cov.:

AF XY:

0.499

AC XY:

37015

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.366

Gnomad4 AMR

AF:

0.597

Gnomad4 ASJ

AF:

0.533

Gnomad4 EAS

AF:

0.427

Gnomad4 SAS

AF:

0.454

Gnomad4 FIN

AF:

0.638

Gnomad4 NFE

AF:

0.527

Gnomad4 OTH

AF:

0.495

Alfa

AF:

0.508

Hom.:

4635

Bravo

AF:

0.482

Asia WGS

AF:

0.473

AC:

1643

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 16, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 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. -

Myosclerosis

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bethlem myopathy 1A

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ullrich congenital muscular dystrophy 1A

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: 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

-0.91

CADD

Benign

0.32

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over