rs117154313

Positions:

• chr21-46111945-G-A

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.116-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,600,712 control chromosomes in the GnomAD database, including 615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (50 hom., cov: 32)
  • Exomes 𝑓: 0.024 (565 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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]

LOC124905043 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 21-46111945-G-A is Benign according to our data. Variant chr21-46111945-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 93901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46111945-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0203 (3084/152262) while in subpopulation NFE AF= 0.0298 (2029/68006). AF 95% confidence interval is 0.0288. There are 50 homozygotes in gnomad4. There are 1504 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 50 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A2	NM_001849.4	c.116-34G>A		intron_variant		ENST00000300527.9
COL6A2	NM_058174.3	c.116-34G>A		intron_variant		ENST00000397763.6
LOC124905043	XR_007067910.1	n.87C>T		non_coding_transcript_exon_variant	1/2
COL6A2	NM_058175.3	c.116-34G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A2	ENST00000300527.9	c.116-34G>A		intron_variant		1	NM_001849.4	P1
COL6A2	ENST00000397763.6	c.116-34G>A		intron_variant		5	NM_058174.3
COL6A2	ENST00000409416.6	c.116-34G>A		intron_variant		5
COL6A2	ENST00000436769.5	c.116-34G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 3083 AN: 152144 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.00447

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0380

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0298

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.0215 AC: 5232 AN: 243146 Hom.: 103 AF XY: 0.0218 AC XY: 2882 AN XY: 132464

Gnomad AFR exome AF: 0.00403

Gnomad AMR exome AF: 0.00707

Gnomad ASJ exome AF: 0.0614

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00648

Gnomad FIN exome AF: 0.0371

Gnomad NFE exome AF: 0.0302

Gnomad OTH exome AF: 0.0200

GnomAD4 exome AF: 0.0242 AC: 35123 AN: 1448450 Hom.: 565 Cov.: 31 AF XY: 0.0239 AC XY: 17258 AN XY: 721196

Gnomad4 AFR exome AF: 0.00351

Gnomad4 AMR exome AF: 0.00774

Gnomad4 ASJ exome AF: 0.0584

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00670

Gnomad4 FIN exome AF: 0.0367

Gnomad4 NFE exome AF: 0.0266

Gnomad4 OTH exome AF: 0.0218

GnomAD4 genome AF: 0.0203 AC: 3084 AN: 152262 Hom.: 50 Cov.: 32 AF XY: 0.0202 AC XY: 1504 AN XY: 74448

Gnomad4 AFR AF: 0.00445

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.0582

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00580

Gnomad4 FIN AF: 0.0380

Gnomad4 NFE AF: 0.0298

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0314 Hom.: 22

Bravo AF: 0.0173

Asia WGS AF: 0.00144 AC: 5 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

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 16, 2012	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 3

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

Publications

LitVar

Other links and lift over

dbSNP: rs117154313; hg19: chr21-47531859;