rs7279347

Variant names:

• chr21-46117968-G-A
• rs7279347
• NM_001849.4:c.1116+32G>A

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.1116+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,598,598 control chromosomes in the GnomAD database, including 212,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19021 hom., cov: 32)
  • Exomes 𝑓: 0.51 (193518 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.08
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 21-46117968-G-A is Benign according to our data. Variant chr21-46117968-G-A is described in ClinVar as Benign. ClinVar VariationId is 93900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4	c.1116+32G>A		intron_variant	Intron 12 of 27	ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.1116+32G>A		intron_variant	Intron 12 of 27		NP_478054.2
COL6A2	NM_058175.3	c.1116+32G>A		intron_variant	Intron 12 of 27		NP_478055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.1116+32G>A		intron_variant	Intron 12 of 27	1	NM_001849.4	ENSP00000300527.4
COL6A2	ENST00000397763.6	c.1116+32G>A		intron_variant	Intron 12 of 27	5		ENSP00000380870.1
COL6A2	ENST00000409416.6	c.1116+32G>A		intron_variant	Intron 11 of 26	5		ENSP00000387115.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74683 AN: 151796 Hom.: 18990 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.495

GnomAD2 exomes AF: 0.529 AC: 124315 AN: 235112 AF XY: 0.522

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.668

Gnomad ASJ exome AF: 0.537

Gnomad EAS exome AF: 0.419

Gnomad FIN exome AF: 0.649

Gnomad NFE exome AF: 0.525

Gnomad OTH exome AF: 0.546

GnomAD4 exome AF: 0.514 AC: 744013 AN: 1446682 Hom.: 193518 Cov.: 32 AF XY: 0.512 AC XY: 367594 AN XY: 717682

African (AFR) AF: 0.352 AC: 11696 AN: 33260

American (AMR) AF: 0.658 AC: 28652 AN: 43530

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 13715 AN: 25688

East Asian (EAS) AF: 0.413 AC: 16196 AN: 39262

South Asian (SAS) AF: 0.447 AC: 37816 AN: 84618

European-Finnish (FIN) AF: 0.634 AC: 32908 AN: 51888

Middle Eastern (MID) AF: 0.461 AC: 2635 AN: 5714

European-Non Finnish (NFE) AF: 0.517 AC: 570231 AN: 1102990

Other (OTH) AF: 0.505 AC: 30164 AN: 59732

GnomAD4 genome AF: 0.492 AC: 74750 AN: 151916 Hom.: 19021 Cov.: 32 AF XY: 0.499 AC XY: 37015 AN XY: 74246

African (AFR) AF: 0.366 AC: 15163 AN: 41460

American (AMR) AF: 0.597 AC: 9132 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1850 AN: 3470

East Asian (EAS) AF: 0.427 AC: 2185 AN: 5112

South Asian (SAS) AF: 0.454 AC: 2186 AN: 4820

European-Finnish (FIN) AF: 0.638 AC: 6755 AN: 10586

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.527 AC: 35769 AN: 67874

Other (OTH) AF: 0.495 AC: 1044 AN: 2110

Alfa AF: 0.504 Hom.: 4686

Bravo AF: 0.482

Asia WGS AF: 0.473 AC: 1643 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Nov 16, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Myosclerosis Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bethlem myopathy 1A Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ullrich congenital muscular dystrophy 1A Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.57
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7279347; hg19: chr21-47537882; COSMIC: COSV56001382; COSMIC: COSV56001382;