21-46126476-T-TGGCCC

Position:

• chr21-46126476-T-TGGCCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001849.4(COL6A2):​c.2423-22_2423-18dupCGGCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00818 in 1,611,530 control chromosomes in the GnomAD database, including 543 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (98 hom., cov: 32)
  • Exomes 𝑓: 0.0069 (445 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.874

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 -10 ACMG points.

• BP6: Variant 21-46126476-T-TGGCCC is Benign according to our data. Variant chr21-46126476-T-TGGCCC is described in ClinVar as [Benign]. Clinvar id is 1241745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A2	NM_001849.4	c.2423-22_2423-18dupCGGCC		intron_variant		ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.2423-22_2423-18dupCGGCC		intron_variant			NP_478054.2
COL6A2	NM_058175.3	c.2423-22_2423-18dupCGGCC		intron_variant			NP_478055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.2423-22_2423-18dupCGGCC		intron_variant		1	NM_001849.4	ENSP00000300527.4
COL6A2	ENST00000397763.6	c.2423-22_2423-18dupCGGCC		intron_variant		5		ENSP00000380870.1
COL6A2	ENST00000409416.6	c.2423-22_2423-18dupCGGCC		intron_variant		5		ENSP00000387115.1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3029 AN: 152114 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00580

Gnomad SAS AF: 0.0863

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00694 AC: 10126 AN: 1459298 Hom.: 445 Cov.: 34 AF XY: 0.00882 AC XY: 6406 AN XY: 726074

Gnomad4 AFR exome AF: 0.0650

Gnomad4 AMR exome AF: 0.00349

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.00179

Gnomad4 SAS exome AF: 0.0770

Gnomad4 FIN exome AF: 0.0000568

Gnomad4 NFE exome AF: 0.000335

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.0200 AC: 3050 AN: 152232 Hom.: 98 Cov.: 32 AF XY: 0.0206 AC XY: 1530 AN XY: 74432

Gnomad4 AFR AF: 0.0589

Gnomad4 AMR AF: 0.00568

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00581

Gnomad4 SAS AF: 0.0862

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.000344 Hom.: 8

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

Mar 21, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs138363207; hg19: chr21-47546390;