rs11089047

Positions:

• chr21-46112606-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.714+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00712 in 1,608,588 control chromosomes in the GnomAD database, including 704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (370 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (334 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.42

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=-0.94).
• BP6: Variant 21-46112606-G-A is Benign according to our data. Variant chr21-46112606-G-A is described in ClinVar as [Benign]. Clinvar id is 93957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46112606-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A2	NM_001849.4	c.714+29G>A		intron_variant		ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.714+29G>A		intron_variant			NP_478054.2
COL6A2	NM_058175.3	c.714+29G>A		intron_variant			NP_478055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.714+29G>A		intron_variant		1	NM_001849.4	ENSP00000300527.4
COL6A2	ENST00000397763.6	c.714+29G>A		intron_variant		5		ENSP00000380870.1
COL6A2	ENST00000409416.6	c.714+29G>A		intron_variant		5		ENSP00000387115.1
COL6A2	ENST00000460886.1	n.160+29G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5693 AN: 151816 Hom.: 368 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0216

GnomAD3 exomes AF: 0.00983 AC: 2384 AN: 242524 Hom.: 132 AF XY: 0.00732 AC XY: 971 AN XY: 132664

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.00683

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000439

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000443

Gnomad OTH exome AF: 0.00301

GnomAD4 exome AF: 0.00394 AC: 5745 AN: 1456656 Hom.: 334 Cov.: 34 AF XY: 0.00337 AC XY: 2440 AN XY: 724626

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.00772

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000529

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000315

Gnomad4 OTH exome AF: 0.00775

GnomAD4 genome AF: 0.0376 AC: 5711 AN: 151932 Hom.: 370 Cov.: 32 AF XY: 0.0357 AC XY: 2649 AN XY: 74250

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.0214

Alfa AF: 0.0226 Hom.: 45

Bravo AF: 0.0432

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

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

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.73

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: rs11089047; hg19: chr21-47532520;