chr21-46132471-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001849.4(COL6A2):c.2979C>T(p.Arg993Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,605,962 control chromosomes in the GnomAD database, including 26,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1768 hom., cov: 34)

Exomes 𝑓: 0.18 ( 25142 hom. )

Consequence

COL6A2
NM_001849.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.00

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 21-46132471-C-T is Benign according to our data. Variant chr21-46132471-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46132471-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4 link	c.2979C>T	p.Arg993Arg	synonymous_variant	Exon 28 of 28	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9 link	c.2979C>T	p.Arg993Arg	synonymous_variant	Exon 28 of 28	1	NM_001849.4	ENSP00000300527.4		P12110-1

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21579

AN:

152170

Hom.:

1770

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.0191

Gnomad SAS

AF:

0.0765

Gnomad FIN

AF:

0.0715

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.131

AC:

31507

AN:

239922

Hom.:

2481

AF XY:

0.134

AC XY:

17553

AN XY:

131024

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.0741

Gnomad ASJ exome

AF:

0.176

Gnomad EAS exome

AF:

0.0244

Gnomad SAS exome

AF:

0.0803

Gnomad FIN exome

AF:

0.0714

Gnomad NFE exome

AF:

0.191

Gnomad OTH exome

AF:

0.149

GnomAD4 exome

AF:

0.177

AC:

257816

AN:

1453674

Hom.:

25142

Cov.:

AF XY:

0.174

AC XY:

126041

AN XY:

722692

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.0788

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.0218

Gnomad4 SAS exome

AF:

0.0796

Gnomad4 FIN exome

AF:

0.0790

Gnomad4 NFE exome

AF:

0.202

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.142

AC:

21578

AN:

152288

Hom.:

1768

Cov.:

AF XY:

0.133

AC XY:

9925

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.174

Gnomad4 EAS

AF:

0.0191

Gnomad4 SAS

AF:

0.0757

Gnomad4 FIN

AF:

0.0715

Gnomad4 NFE

AF:

0.194

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.187

Hom.:

3128

Bravo

AF:

0.144

Asia WGS

AF:

0.0690

AC:

240

AN:

3478

EpiCase

AF:

0.200

EpiControl

AF:

0.196

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Sep 19, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

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

- -

Dec 01, 2015

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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Myosclerosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Glutamate formiminotransferase deficiency

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bethlem myopathy 1A

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Collagen 6-related myopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.6

DANN

Benign

0.92

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