rs111592472

Positions:

• chr21-46117958-C-T
• chr21-46117958-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001849.4(COL6A2):​c.1116+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,602,654 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (40 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (31 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0870

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=-0.86).
• BP6: Variant 21-46117958-C-T is Benign according to our data. Variant chr21-46117958-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0123 (1870/152142) while in subpopulation AFR AF= 0.0407 (1689/41524). AF 95% confidence interval is 0.0391. There are 40 homozygotes in gnomad4. There are 877 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 40 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A2	NM_001849.4	c.1116+22C>T		intron_variant		ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.1116+22C>T		intron_variant			NP_478054.2
COL6A2	NM_058175.3	c.1116+22C>T		intron_variant			NP_478055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.1116+22C>T		intron_variant		1	NM_001849.4	ENSP00000300527.4
COL6A2	ENST00000397763.6	c.1116+22C>T		intron_variant		5		ENSP00000380870.1
COL6A2	ENST00000409416.6	c.1116+22C>T		intron_variant		5		ENSP00000387115.1

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1868 AN: 152024 Hom.: 40 Cov.: 33

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00341 AC: 818 AN: 239790 Hom.: 13 AF XY: 0.00251 AC XY: 326 AN XY: 129936

Gnomad AFR exome AF: 0.0395

Gnomad AMR exome AF: 0.00422

Gnomad ASJ exome AF: 0.000105

Gnomad EAS exome AF: 0.0000558

Gnomad SAS exome AF: 0.000206

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000471

Gnomad OTH exome AF: 0.00242

GnomAD4 exome AF: 0.00151 AC: 2186 AN: 1450512 Hom.: 31 Cov.: 32 AF XY: 0.00131 AC XY: 942 AN XY: 719852

Gnomad4 AFR exome AF: 0.0400

Gnomad4 AMR exome AF: 0.00496

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.000235

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000321

Gnomad4 OTH exome AF: 0.00388

GnomAD4 genome AF: 0.0123 AC: 1870 AN: 152142 Hom.: 40 Cov.: 33 AF XY: 0.0118 AC XY: 877 AN XY: 74376

Gnomad4 AFR AF: 0.0407

Gnomad4 AMR AF: 0.00830

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.00481 Hom.: 0

Bravo AF: 0.0141

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely 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	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.73
DANN	Benign	0.66

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: rs111592472; hg19: chr21-47537872;