rs79205686

Variant names:

• chr21-46124614-G-T
• rs79205686
• NM_001849.4:c.1672-37G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-46124614-G-T
• chr21-46124614-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001849.4(COL6A2):​c.1672-37G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 1,606,578 control chromosomes in the GnomAD database, including 6,032 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (326 hom., cov: 33)
  • Exomes 𝑓: 0.084 (5706 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.364
• Publications: 4 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, SD, 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: AR, AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 21-46124614-G-T is Benign according to our data. Variant chr21-46124614-G-T is described in ClinVar as Benign. ClinVar VariationId is 93917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

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.1672-37G>T		intron	N/A	NP_001840.3
	COL6A2	NM_058174.3	MANE Plus Clinical	c.1672-37G>T		intron	N/A	NP_478054.2	P12110-2
	COL6A2	NM_058175.3		c.1672-37G>T		intron	N/A	NP_478055.2	P12110-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A2	ENST00000300527.9	TSL:1 MANE Select	c.1672-37G>T		intron	N/A	ENSP00000300527.4	P12110-1
	COL6A2	ENST00000397763.6	TSL:5 MANE Plus Clinical	c.1672-37G>T		intron	N/A	ENSP00000380870.1	P12110-2
	COL6A2	ENST00000857098.1		c.1867-37G>T		intron	N/A	ENSP00000527157.1

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 8783 AN: 151964 Hom.: 327 Cov.: 33

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.0624

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0904

Gnomad OTH AF: 0.0674

GnomAD2 exomes AF: 0.0634 AC: 15765 AN: 248770 AF XY: 0.0663

Gnomad AFR exome AF: 0.0191

Gnomad AMR exome AF: 0.0369

Gnomad ASJ exome AF: 0.0783

Gnomad EAS exome AF: 0.0234

Gnomad FIN exome AF: 0.0269

Gnomad NFE exome AF: 0.0896

Gnomad OTH exome AF: 0.0684

GnomAD4 exome AF: 0.0840 AC: 122160 AN: 1454492 Hom.: 5706 Cov.: 29 AF XY: 0.0835 AC XY: 60474 AN XY: 724016

African (AFR) AF: 0.0159 AC: 530 AN: 33340

American (AMR) AF: 0.0388 AC: 1735 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 2097 AN: 26070

East Asian (EAS) AF: 0.0214 AC: 848 AN: 39668

South Asian (SAS) AF: 0.0627 AC: 5402 AN: 86122

European-Finnish (FIN) AF: 0.0290 AC: 1518 AN: 52292

Middle Eastern (MID) AF: 0.115 AC: 656 AN: 5722

European-Non Finnish (NFE) AF: 0.0946 AC: 104656 AN: 1106510

Other (OTH) AF: 0.0785 AC: 4718 AN: 60086

GnomAD4 genome AF: 0.0577 AC: 8779 AN: 152086 Hom.: 326 Cov.: 33 AF XY: 0.0544 AC XY: 4041 AN XY: 74338

African (AFR) AF: 0.0184 AC: 762 AN: 41488

American (AMR) AF: 0.0447 AC: 684 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5168

South Asian (SAS) AF: 0.0623 AC: 300 AN: 4816

European-Finnish (FIN) AF: 0.0271 AC: 287 AN: 10610

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0904 AC: 6140 AN: 67928

Other (OTH) AF: 0.0662 AC: 140 AN: 2114

Alfa AF: 0.0260 Hom.: 56

Bravo AF: 0.0579

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.24
DANN	Benign	0.70
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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: rs79205686; hg19: chr21-47544528;