21-46098272-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001849.4(COL6A2):c.-28+99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,254 control chromosomes in the GnomAD database, including 54,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (54468 hom., cov: 34)
  • Exomes 𝑓: 0.87 (183 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 21-46098272-T-C is Benign according to our data. Variant chr21-46098272-T-C is described in ClinVar as [Benign]. Clinvar id is 1231952.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A2	NM_001849.4	c.-28+99T>C		intron_variant		ENST00000300527.9
COL6A2	NM_058174.3	c.-28+99T>C		intron_variant		ENST00000397763.6
COL6A2	NM_058175.3	c.-28+99T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A2	ENST00000300527.9	c.-28+99T>C		intron_variant		1	NM_001849.4	P1
COL6A2	ENST00000397763.6	c.-28+99T>C		intron_variant		5	NM_058174.3

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128256 AN: 151668 Hom.: 54438 Cov.: 34

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.831

GnomAD4 exome AF: 0.872 AC: 415 AN: 476 Hom.: 183 AF XY: 0.880 AC XY: 257 AN XY: 292

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.886

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.888

Gnomad4 OTH exome AF: 0.857

GnomAD4 genome AF: 0.846 AC: 128336 AN: 151778 Hom.: 54468 Cov.: 34 AF XY: 0.848 AC XY: 62944 AN XY: 74190

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.847

Gnomad4 ASJ AF: 0.885

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.896

Gnomad4 FIN AF: 0.939

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.830

Alfa AF: 0.844 Hom.: 2718

Bravo AF: 0.833

Asia WGS AF: 0.796 AC: 2649 AN: 3326

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.5
Dann	Benign	0.39

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: rs2277817; hg19: chr21-47518186;