chr21-46124627-C-G

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.1672-24C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,610,766 control chromosomes in the GnomAD database, including 195,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.45 ( 16417 hom., cov: 32)

Exomes 𝑓: 0.49 ( 178595 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.789

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

This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 21-46124627-C-G is Benign according to our data. Variant chr21-46124627-C-G is described in ClinVar as [Benign]. Clinvar id is 93916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46124627-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4 link	c.1672-24C>G	intron_variant	Intron 21 of 27	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3
COL6A2	NM_058174.3 link	c.1672-24C>G	intron_variant	Intron 21 of 27		NP_478054.2	P12110-2
COL6A2	NM_058175.3 link	c.1672-24C>G	intron_variant	Intron 21 of 27		NP_478055.2	P12110-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL6A2	ENST00000300527.9 link	c.1672-24C>G	intron_variant	Intron 21 of 27	1	NM_001849.4	ENSP00000300527.4	P12110-1
COL6A2	ENST00000397763.6 link	c.1672-24C>G	intron_variant	Intron 21 of 27	5		ENSP00000380870.1	P12110-2
COL6A2	ENST00000409416.6 link	c.1672-24C>G	intron_variant	Intron 20 of 26	5		ENSP00000387115.1	P12110-3
COL6A2	ENST00000413758.1 link	c.295-24C>G	intron_variant	Intron 6 of 10	3		ENSP00000395751.1	H7C0M5

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67700

AN:

151794

Hom.:

16402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.582

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.618

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.510

Gnomad OTH

AF:

0.460

GnomAD3 exomes

AF:

0.493

AC:

122940

AN:

249358

Hom.:

32120

AF XY:

0.483

AC XY:

65406

AN XY:

135428

show subpopulations

Gnomad AFR exome

AF:

0.242

Gnomad AMR exome

AF:

0.654

Gnomad ASJ exome

AF:

0.516

Gnomad EAS exome

AF:

0.443

Gnomad SAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.624

Gnomad NFE exome

AF:

0.504

Gnomad OTH exome

AF:

0.517

GnomAD4 exome

AF:

0.489

AC:

713094

AN:

1458852

Hom.:

178595

Cov.:

AF XY:

0.484

AC XY:

351331

AN XY:

725828

show subpopulations

Gnomad4 AFR exome

AF:

0.229

Gnomad4 AMR exome

AF:

0.645

Gnomad4 ASJ exome

AF:

0.517

Gnomad4 EAS exome

AF:

0.436

Gnomad4 SAS exome

AF:

0.331

Gnomad4 FIN exome

AF:

0.615

Gnomad4 NFE exome

AF:

0.499

Gnomad4 OTH exome

AF:

0.478

GnomAD4 genome

AF:

0.446

AC:

67732

AN:

151914

Hom.:

16417

Cov.:

AF XY:

0.451

AC XY:

33505

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.578

Gnomad4 ASJ

AF:

0.520

Gnomad4 EAS

AF:

0.453

Gnomad4 SAS

AF:

0.333

Gnomad4 FIN

AF:

0.618

Gnomad4 NFE

AF:

0.510

Gnomad4 OTH

AF:

0.455

Alfa

AF:

0.414

Hom.:

2163

Bravo

AF:

0.437

Asia WGS

AF:

0.403

AC:

1401

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

Nov 16, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.73

CADD

Benign

DANN

Benign

0.78

BranchPoint Hunter

4.0

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

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