rs7279347

Positions:

• chr21-46117968-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 93900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46117968-G-A is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
COL6A2	NM_001849.4	c.1116+32G>A		intron_variant		ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.1116+32G>A		intron_variant		ENST00000397763.6	NP_478054.2
COL6A2	NM_058175.3	c.1116+32G>A		intron_variant			NP_478055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.1116+32G>A		intron_variant		1	NM_001849.4	ENSP00000300527	P1
COL6A2	ENST00000397763.6	c.1116+32G>A		intron_variant		5	NM_058174.3	ENSP00000380870
COL6A2	ENST00000409416.6	c.1116+32G>A		intron_variant		5		ENSP00000387115

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

GnomAD3 exomes AF: 0.529 AC: 124315 AN: 235112 Hom.: 33538 AF XY: 0.522 AC XY: 66552 AN XY: 127376

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 SAS exome AF: 0.448

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

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.658

Gnomad4 ASJ exome AF: 0.534

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.634

Gnomad4 NFE exome AF: 0.517

Gnomad4 OTH exome AF: 0.505

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

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.495

Alfa AF: 0.508 Hom.: 4635

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

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 16, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 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. -

Myosclerosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Bethlem myopathy 1A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Ullrich congenital muscular dystrophy 1A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs7279347; hg19: chr21-47537882; COSMIC: COSV56001382; COSMIC: COSV56001382;