rs55933135

Positions:

• chr21-46124748-A-G

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.1734+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,607,886 control chromosomes in the GnomAD database, including 11,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2487 hom., cov: 33)
  • Exomes 𝑓: 0.098 (8638 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.10

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=-0.97).
• BP6: Variant 21-46124748-A-G is Benign according to our data. Variant chr21-46124748-A-G is described in ClinVar as [Benign]. Clinvar id is 93918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46124748-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A2	NM_001849.4	c.1734+35A>G		intron_variant		ENST00000300527.9
COL6A2	NM_058174.3	c.1734+35A>G		intron_variant		ENST00000397763.6
COL6A2	NM_058175.3	c.1734+35A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A2	ENST00000300527.9	c.1734+35A>G		intron_variant		1	NM_001849.4	P1
COL6A2	ENST00000397763.6	c.1734+35A>G		intron_variant		5	NM_058174.3
COL6A2	ENST00000409416.6	c.1734+35A>G		intron_variant		5
COL6A2	ENST00000413758.1	c.357+35A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22312 AN: 151794 Hom.: 2475 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0684

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0916

Gnomad OTH AF: 0.130

GnomAD3 exomes AF: 0.0964 AC: 23861 AN: 247630 Hom.: 1796 AF XY: 0.0968 AC XY: 13024 AN XY: 134480

Gnomad AFR exome AF: 0.324

Gnomad AMR exome AF: 0.0510

Gnomad ASJ exome AF: 0.0790

Gnomad EAS exome AF: 0.0266

Gnomad SAS exome AF: 0.148

Gnomad FIN exome AF: 0.0266

Gnomad NFE exome AF: 0.0906

Gnomad OTH exome AF: 0.0838

GnomAD4 exome AF: 0.0982 AC: 142914 AN: 1455970 Hom.: 8638 Cov.: 33 AF XY: 0.0987 AC XY: 71510 AN XY: 724474

Gnomad4 AFR exome AF: 0.332

Gnomad4 AMR exome AF: 0.0553

Gnomad4 ASJ exome AF: 0.0810

Gnomad4 EAS exome AF: 0.0226

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.0291

Gnomad4 NFE exome AF: 0.0952

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.147 AC: 22364 AN: 151916 Hom.: 2487 Cov.: 33 AF XY: 0.142 AC XY: 10528 AN XY: 74256

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.0775

Gnomad4 ASJ AF: 0.0784

Gnomad4 EAS AF: 0.0254

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.0271

Gnomad4 NFE AF: 0.0916

Gnomad4 OTH AF: 0.134

Alfa AF: 0.112 Hom.: 256

Bravo AF: 0.157

Asia WGS AF: 0.134 AC: 469 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	Jun 19, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.41
DANN	Benign	0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs55933135; hg19: chr21-47544662;