rs201367713

Variant names:

• chr21-46126455-C-T
• rs201367713
• NM_001849.4:c.2423-48C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001849.4(COL6A2):​c.2423-48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,610,072 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (8 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.20
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• collagen 6-related myopathy

  Inheritance: AD, AR Classification: DEFINITIVE Submitted by: ClinGen
• Ullrich congenital muscular dystrophy 1B

  Inheritance: AR, AD Classification: DEFINITIVE Submitted by: G2P
• Bethlem myopathy 1A

  Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp
• Ullrich congenital muscular dystrophy 1A

  Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Bethlem myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Ullrich congenital muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• myosclerosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 21-46126455-C-T is Benign according to our data. Variant chr21-46126455-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 258325.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001849.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A2	NM_001849.4	MANE Select	c.2423-48C>T		intron	N/A	NP_001840.3
	COL6A2	NM_058174.3	MANE Plus Clinical	c.2423-48C>T		intron	N/A	NP_478054.2
	COL6A2	NM_058175.3		c.2423-48C>T		intron	N/A	NP_478055.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A2	ENST00000300527.9	TSL:1 MANE Select	c.2423-48C>T		intron	N/A	ENSP00000300527.4
	COL6A2	ENST00000397763.6	TSL:5 MANE Plus Clinical	c.2423-48C>T		intron	N/A	ENSP00000380870.1
	COL6A2	ENST00000857098.1		c.2618-48C>T		intron	N/A	ENSP00000527157.1

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 264 AN: 152110 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00155 AC: 384 AN: 248500 AF XY: 0.00145

Gnomad AFR exome AF: 0.000556

Gnomad AMR exome AF: 0.000639

Gnomad ASJ exome AF: 0.000405

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00296

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00254 AC: 3698 AN: 1457844 Hom.: 8 Cov.: 33 AF XY: 0.00241 AC XY: 1751 AN XY: 725436

African (AFR) AF: 0.000658 AC: 22 AN: 33422

American (AMR) AF: 0.000895 AC: 40 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.000498 AC: 13 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86202

European-Finnish (FIN) AF: 0.000152 AC: 8 AN: 52662

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00312 AC: 3455 AN: 1109072

Other (OTH) AF: 0.00257 AC: 155 AN: 60266

GnomAD4 genome AF: 0.00173 AC: 264 AN: 152228 Hom.: 1 Cov.: 33 AF XY: 0.00155 AC XY: 115 AN XY: 74428

African (AFR) AF: 0.000530 AC: 22 AN: 41516

American (AMR) AF: 0.00216 AC: 33 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00297 AC: 202 AN: 68008

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00197 Hom.: 0

Bravo AF: 0.00198

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.95
DANN	Benign	0.47
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201367713; hg19: chr21-47546369; COSMIC: COSV55998367; COSMIC: COSV55998367;