Variant 21-46132261-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001849.4(COL6A2):c.2769C>T(p.His923=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00912 in 1,606,208 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 6 hom., cov: 34)

Exomes 𝑓: 0.0095 ( 77 hom. )

Consequence

COL6A2
NM_001849.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.824

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 21-46132261-C-T is Benign according to our data. Variant chr21-46132261-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46132261-C-T is described in Lovd as [Benign]. Variant chr21-46132261-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.824 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A2	NM_001849.4 linkuse as main transcript	c.2769C>T	p.His923=	synonymous_variant	28/28	ENST00000300527.9	NP_001840.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9 linkuse as main transcript	c.2769C>T	p.His923=	synonymous_variant	28/28	1	NM_001849.4	ENSP00000300527	P1	P12110-1

Frequencies

GnomAD3 genomes

AF:

0.00574

AC:

873

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00415

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00996

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00507

AC:

1198

AN:

236200

Hom.:

AF XY:

0.00511

AC XY:

661

AN XY:

129304

show subpopulations

Gnomad AFR exome

AF:

0.00182

Gnomad AMR exome

AF:

0.00204

Gnomad ASJ exome

AF:

0.00472

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000401

Gnomad FIN exome

AF:

0.00312

Gnomad NFE exome

AF:

0.00900

Gnomad OTH exome

AF:

0.00444

GnomAD4 exome

AF:

0.00947

AC:

13774

AN:

1453880

Hom.:

Cov.:

AF XY:

0.00913

AC XY:

6602

AN XY:

723356

show subpopulations

Gnomad4 AFR exome

AF:

0.00165

Gnomad4 AMR exome

AF:

0.00232

Gnomad4 ASJ exome

AF:

0.00481

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000525

Gnomad4 FIN exome

AF:

0.00366

Gnomad4 NFE exome

AF:

0.0115

Gnomad4 OTH exome

AF:

0.00723

GnomAD4 genome

AF:

0.00573

AC:

873

AN:

152328

Hom.:

Cov.:

AF XY:

0.00537

AC XY:

400

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00212

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00415

Gnomad4 NFE

AF:

0.00997

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00635

Hom.:

Bravo

AF:

0.00539

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 16, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 26, 2021	This variant is associated with the following publications: (PMID: 15689448) -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	COL6A2: BP4, BP7, BS1, BS2 -

Myosclerosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Bethlem myopathy 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 28, 2024

- -

Collagen 6-related myopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

1.1

DANN

Benign

0.84

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