rs201367713

chr21-46126455-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001849.4(COL6A2):c.2423-48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,610,072 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (8 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.20

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 21-46126455-C-T is Benign according to our data. Variant chr21-46126455-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258325.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A2	NM_001849.4	c.2423-48C>T		intron_variant		ENST00000300527.9
COL6A2	NM_058174.3	c.2423-48C>T		intron_variant		ENST00000397763.6
COL6A2	NM_058175.3	c.2423-48C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A2	ENST00000300527.9	c.2423-48C>T		intron_variant		1	NM_001849.4	P1
COL6A2	ENST00000397763.6	c.2423-48C>T		intron_variant		5	NM_058174.3
COL6A2	ENST00000409416.6	c.2423-48C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 264 AN: 152110 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00155 AC: 384 AN: 248500 Hom.: 1 AF XY: 0.00145 AC XY: 195 AN XY: 134424

Gnomad AFR exome AF: 0.000556

Gnomad AMR exome AF: 0.000639

Gnomad ASJ exome AF: 0.000405

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.0000331

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00296

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00254 AC: 3698 AN: 1457844 Hom.: 8 Cov.: 33 AF XY: 0.00241 AC XY: 1751 AN XY: 725436

Gnomad4 AFR exome AF: 0.000658

Gnomad4 AMR exome AF: 0.000895

Gnomad4 ASJ exome AF: 0.000498

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.000152

Gnomad4 NFE exome AF: 0.00312

Gnomad4 OTH exome AF: 0.00257

GnomAD4 genome AF: 0.00173 AC: 264 AN: 152228 Hom.: 1 Cov.: 33 AF XY: 0.00155 AC XY: 115 AN XY: 74428

Gnomad4 AFR AF: 0.000530

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00297

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00197 Hom.: 0

Bravo AF: 0.00198

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.95
Dann	Benign	0.47

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: rs201367713; hg19: chr21-47546369; COSMIC: COSV55998367; COSMIC: COSV55998367;