21-46126476-T-TGGCCCGGCCCGGCCC

Position:

• chr21-46126476-T-TGGCCCGGCCCGGCCC

Variant summary

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

The NM_001849.4(COL6A2):​c.2423-18_2423-17insCGGCCCGGCCCGGCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 152,210 control chromosomes in the GnomAD database, including 265 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.051 (265 hom., cov: 32)
  • Exomes 𝑓: 0.073 (4488 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Likely 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-TGGCCCGGCCCGGCCC is Benign according to our data. Variant chr21-46126476-T-TGGCCCGGCCCGGCCC is described in ClinVar as [Likely_benign]. Clinvar id is 258324.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A2	NM_001849.4	c.2423-18_2423-17insCGGCCCGGCCCGGCC		intron_variant		ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.2423-18_2423-17insCGGCCCGGCCCGGCC		intron_variant			NP_478054.2
COL6A2	NM_058175.3	c.2423-18_2423-17insCGGCCCGGCCCGGCC		intron_variant			NP_478055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.2423-18_2423-17insCGGCCCGGCCCGGCC		intron_variant		1	NM_001849.4	ENSP00000300527.4
COL6A2	ENST00000397763.6	c.2423-18_2423-17insCGGCCCGGCCCGGCC		intron_variant		5		ENSP00000380870.1
COL6A2	ENST00000409416.6	c.2423-18_2423-17insCGGCCCGGCCCGGCC		intron_variant		5		ENSP00000387115.1

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 7773 AN: 152092 Hom.: 267 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.0420

Gnomad ASJ AF: 0.0753

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.0607

Gnomad FIN AF: 0.0226

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.0593

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0731 AC: 106489 AN: 1457208 Hom.: 4488 Cov.: 34 AF XY: 0.0730 AC XY: 52954 AN XY: 725056

Gnomad4 AFR exome AF: 0.0137

Gnomad4 AMR exome AF: 0.0356

Gnomad4 ASJ exome AF: 0.0754

Gnomad4 EAS exome AF: 0.0211

Gnomad4 SAS exome AF: 0.0618

Gnomad4 FIN exome AF: 0.0245

Gnomad4 NFE exome AF: 0.0813

Gnomad4 OTH exome AF: 0.0704

GnomAD4 genome AF: 0.0510 AC: 7765 AN: 152210 Hom.: 265 Cov.: 32 AF XY: 0.0479 AC XY: 3567 AN XY: 74420

Gnomad4 AFR AF: 0.0151

Gnomad4 AMR AF: 0.0420

Gnomad4 ASJ AF: 0.0753

Gnomad4 EAS AF: 0.0186

Gnomad4 SAS AF: 0.0605

Gnomad4 FIN AF: 0.0226

Gnomad4 NFE AF: 0.0793

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0134 Hom.: 8

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

Apr 15, 2016

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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;