2-237324840-G-A

Position:

chr2-237324840-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004369.4(COL6A3):c.9494-26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,610,050 control chromosomes in the GnomAD database, including 75,182 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 0.26 ( 5743 hom., cov: 31)

Exomes 𝑓: 0.31 ( 69439 hom. )

Consequence

COL6A3
NM_004369.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.91

Variant links:

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]

COL6A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-237324840-G-A is Benign according to our data. Variant chr2-237324840-G-A is described in ClinVar as [Benign]. Clinvar id is 95022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-237324840-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
COL6A3	NM_004369.4 linkuse as main transcript	c.9494-26C>T	intron_variant	ENST00000295550.9	NP_004360.2
COL6A3	NM_057166.5 linkuse as main transcript	c.7673-26C>T	intron_variant		NP_476507.3
COL6A3	NM_057167.4 linkuse as main transcript	c.8876-26C>T	intron_variant		NP_476508.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A3	ENST00000295550.9 linkuse as main transcript	c.9494-26C>T		intron_variant		1	NM_004369.4	ENSP00000295550	P1	P12111-1

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39597

AN:

151772

Hom.:

5748

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.341

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.265

GnomAD3 exomes

AF:

0.290

AC:

71466

AN:

246308

Hom.:

10837

AF XY:

0.294

AC XY:

39200

AN XY:

133428

show subpopulations

Gnomad AFR exome

AF:

0.127

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.317

Gnomad EAS exome

AF:

0.321

Gnomad SAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.355

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.305

AC:

445269

AN:

1458160

Hom.:

69439

Cov.:

AF XY:

0.305

AC XY:

221349

AN XY:

725456

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.256

Gnomad4 ASJ exome

AF:

0.317

Gnomad4 EAS exome

AF:

0.389

Gnomad4 SAS exome

AF:

0.257

Gnomad4 FIN exome

AF:

0.348

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.290

GnomAD4 genome

AF:

0.261

AC:

39594

AN:

151890

Hom.:

5743

Cov.:

AF XY:

0.263

AC XY:

19539

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.266

Gnomad4 ASJ

AF:

0.333

Gnomad4 EAS

AF:

0.342

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.351

Gnomad4 NFE

AF:

0.315

Gnomad4 OTH

AF:

0.263

Alfa

AF:

0.303

Hom.:

2674

Bravo

AF:

0.249

Asia WGS

AF:

0.254

AC:

886

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 31, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 40. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 02, 2012	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.45

DANN

Benign

0.88

BranchPoint Hunter

0.0

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