21-46122464-C-T

Variant names:

• chr21-46122464-C-T
• rs17272651
• NM_001849.4:c.1573-32C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001849.4(COL6A2):​c.1573-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0813 in 1,612,192 control chromosomes in the GnomAD database, including 6,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (327 hom., cov: 32)
  • Exomes 𝑓: 0.084 (5722 hom.)
• Consequence: COL6A2 NM_001849.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.18

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=-0.79).
• BP6: Variant 21-46122464-C-T is Benign according to our data. Variant chr21-46122464-C-T is described in ClinVar as [Benign]. Clinvar id is 93912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46122464-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4	c.1573-32C>T		intron_variant	Intron 19 of 27	ENST00000300527.9	NP_001840.3
COL6A2	NM_058174.3	c.1573-32C>T		intron_variant	Intron 19 of 27		NP_478054.2
COL6A2	NM_058175.3	c.1573-32C>T		intron_variant	Intron 19 of 27		NP_478055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9	c.1573-32C>T		intron_variant	Intron 19 of 27	1	NM_001849.4	ENSP00000300527.4
COL6A2	ENST00000397763.6	c.1573-32C>T		intron_variant	Intron 19 of 27	5		ENSP00000380870.1
COL6A2	ENST00000409416.6	c.1573-32C>T		intron_variant	Intron 18 of 26	5		ENSP00000387115.1
COL6A2	ENST00000413758.1	c.196-32C>T		intron_variant	Intron 4 of 10	3		ENSP00000395751.1

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 8747 AN: 152066 Hom.: 329 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.0783

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0905

Gnomad OTH AF: 0.0675

GnomAD3 exomes AF: 0.0630 AC: 15735 AN: 249836 Hom.: 627 AF XY: 0.0660 AC XY: 8953 AN XY: 135604

Gnomad AFR exome AF: 0.0180

Gnomad AMR exome AF: 0.0366

Gnomad ASJ exome AF: 0.0781

Gnomad EAS exome AF: 0.0235

Gnomad SAS exome AF: 0.0630

Gnomad FIN exome AF: 0.0258

Gnomad NFE exome AF: 0.0895

Gnomad OTH exome AF: 0.0682

GnomAD4 exome AF: 0.0838 AC: 122394 AN: 1460008 Hom.: 5722 Cov.: 34 AF XY: 0.0834 AC XY: 60552 AN XY: 726292

Gnomad4 AFR exome AF: 0.0150

Gnomad4 AMR exome AF: 0.0386

Gnomad4 ASJ exome AF: 0.0804

Gnomad4 EAS exome AF: 0.0214

Gnomad4 SAS exome AF: 0.0624

Gnomad4 FIN exome AF: 0.0279

Gnomad4 NFE exome AF: 0.0945

Gnomad4 OTH exome AF: 0.0784

GnomAD4 genome AF: 0.0574 AC: 8739 AN: 152184 Hom.: 327 Cov.: 32 AF XY: 0.0540 AC XY: 4015 AN XY: 74402

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.0448

Gnomad4 ASJ AF: 0.0783

Gnomad4 EAS AF: 0.0196

Gnomad4 SAS AF: 0.0627

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.0905

Gnomad4 OTH AF: 0.0664

Alfa AF: 0.0744 Hom.: 107

Bravo AF: 0.0576

Asia WGS AF: 0.0460 AC: 162 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 16, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.8
DANN	Benign	0.73

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: rs17272651; hg19: chr21-47542378;