chr2-237363239-T-TA

Position:

• chr2-237363239-T-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004369.4(COL6A3):​c.6063+13dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,610,626 control chromosomes in the GnomAD database, including 27,850 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3005 hom., cov: 27)
  • Exomes 𝑓: 0.18 (24845 hom.)
• Consequence: COL6A3 NM_004369.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.523

Genes affected

COL6A3 (HGNC:2213): (collagen type VI alpha 3 chain) This gene encodes the alpha-3 chain, one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The alpha-3 chain of type VI collagen is much larger than the alpha-1 and -2 chains. This difference in size is largely due to an increase in the number of subdomains, similar to von Willebrand Factor type A domains, that are found in the amino terminal globular domain of all the alpha chains. 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 the type VI collagen genes are associated with Bethlem myopathy, a rare autosomal dominant proximal myopathy with early childhood onset. Mutations in this gene are also a cause of Ullrich congenital muscular dystrophy, also referred to as Ullrich scleroatonic muscular dystrophy, an autosomal recessive congenital myopathy that is more severe than Bethlem myopathy. Multiple transcript variants have been identified, but the full-length nature of only some of these variants has been described. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-237363239-T-TA is Benign according to our data. Variant chr2-237363239-T-TA is described in ClinVar as [Benign]. Clinvar id is 94950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A3	NM_004369.4	c.6063+13dupT		intron_variant		ENST00000295550.9	NP_004360.2
COL6A3	NM_057167.4	c.5445+13dupT		intron_variant			NP_476508.2
COL6A3	NM_057166.5	c.4242+13dupT		intron_variant			NP_476507.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A3	ENST00000295550.9	c.6063+13dupT		intron_variant		1	NM_004369.4	ENSP00000295550.4
COL6A3	ENST00000472056.5	c.4242+13dupT		intron_variant		1		ENSP00000418285.1
COL6A3	ENST00000353578.9	c.5445+13dupT		intron_variant		5		ENSP00000315873.4

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29119 AN: 150860 Hom.: 3002 Cov.: 27

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00391

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.199

GnomAD3 exomes AF: 0.155 AC: 38978 AN: 251318 Hom.: 3522 AF XY: 0.155 AC XY: 21088 AN XY: 135836

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.0939

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.00304

Gnomad SAS exome AF: 0.106

Gnomad FIN exome AF: 0.185

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.180 AC: 262175 AN: 1459648 Hom.: 24845 Cov.: 33 AF XY: 0.177 AC XY: 128797 AN XY: 726216

Gnomad4 AFR exome AF: 0.254

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.00182

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.193 AC: 29151 AN: 150978 Hom.: 3005 Cov.: 27 AF XY: 0.190 AC XY: 13985 AN XY: 73658

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.00392

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.198

Asia WGS AF: 0.0580 AC: 206 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Eurofins Ntd Llc (ga)	Nov 05, 2012	- -

Bethlem myopathy 1A Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Collagen 6-related myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs11385011; hg19: chr2-238271882;