rs10202497

Positions:

• chr2-237362251-C-A
• chr2-237362251-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004369.4(COL6A3):​c.6064-420G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,162 control chromosomes in the GnomAD database, including 2,067 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2067 hom., cov: 32)
• Consequence: COL6A3 NM_004369.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A3	NM_004369.4	c.6064-420G>T		intron_variant		ENST00000295550.9
COL6A3	NM_057166.5	c.4243-420G>T		intron_variant
COL6A3	NM_057167.4	c.5446-420G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A3	ENST00000295550.9	c.6064-420G>T		intron_variant		1	NM_004369.4	P1
COL6A3	ENST00000472056.5	c.4243-420G>T		intron_variant		1
COL6A3	ENST00000353578.9	c.5446-420G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23766 AN: 152044 Hom.: 2061 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0455

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.167

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.156 AC: 23791 AN: 152162 Hom.: 2067 Cov.: 32 AF XY: 0.156 AC XY: 11566 AN XY: 74370

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.0454

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.165

Alfa AF: 0.131 Hom.: 1165

Bravo AF: 0.161

Asia WGS AF: 0.103 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.0
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10202497; hg19: chr2-238270894;