rs138312213

Variant names:

• chr21-46112346-C-T
• rs138312213
• NM_001849.4:c.483C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-46112346-C-T
• chr21-46112346-C-A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001849.4(COL6A2):​c.483C>T​(p.Thr161Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000385 in 1,609,606 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (4 hom.)
• Consequence: COL6A2 NM_001849.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.15
• 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, 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 21-46112346-C-T is Benign according to our data. Variant chr21-46112346-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 196331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.15 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 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.483C>T	p.Thr161Thr	synonymous	Exon 3 of 28	NP_001840.3
	COL6A2	NM_058174.3	MANE Plus Clinical	c.483C>T	p.Thr161Thr	synonymous	Exon 3 of 28	NP_478054.2	P12110-2
	COL6A2	NM_058175.3		c.483C>T	p.Thr161Thr	synonymous	Exon 3 of 28	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.483C>T	p.Thr161Thr	synonymous	Exon 3 of 28	ENSP00000300527.4	P12110-1
	COL6A2	ENST00000397763.6	TSL:5 MANE Plus Clinical	c.483C>T	p.Thr161Thr	synonymous	Exon 3 of 28	ENSP00000380870.1	P12110-2
	COL6A2	ENST00000857098.1		c.483C>T	p.Thr161Thr	synonymous	Exon 3 of 28	ENSP00000527157.1

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 265 AN: 152124 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00618

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000544 AC: 130 AN: 239014 AF XY: 0.000411

Gnomad AFR exome AF: 0.00654

Gnomad AMR exome AF: 0.000702

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000564

Gnomad OTH exome AF: 0.000511

GnomAD4 exome AF: 0.000238 AC: 347 AN: 1457364 Hom.: 4 Cov.: 33 AF XY: 0.000211 AC XY: 153 AN XY: 724722

African (AFR) AF: 0.00703 AC: 235 AN: 33406

American (AMR) AF: 0.000740 AC: 33 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51056

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5760

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1110584

Other (OTH) AF: 0.000831 AC: 50 AN: 60192

GnomAD4 genome AF: 0.00179 AC: 272 AN: 152242 Hom.: 1 Cov.: 32 AF XY: 0.00173 AC XY: 129 AN XY: 74436

African (AFR) AF: 0.00633 AC: 263 AN: 41550

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.000246 Hom.: 0

Bravo AF: 0.00198

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Bethlem myopathy 1A (1)
-	-	1	Collagen 6-related myopathy (1)
-	-	1	Myosclerosis (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.5
DANN	Benign	0.85
PhyloP100		-3.2
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: rs138312213; hg19: chr21-47532260;