rs140419176

chr21-46132261-C-Tchr21-46132261-C-Achr21-46132261-C-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001849.4(COL6A2):c.2769C>T(p.His923=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00912 in 1,606,208 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (6 hom., cov: 34)
  • Exomes 𝑓: 0.0095 (77 hom.)
• Consequence: COL6A2 NM_001849.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.824

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 21-46132261-C-T is Benign according to our data. Variant chr21-46132261-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46132261-C-T is described in Lovd as [Benign]. Variant chr21-46132261-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.824 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A2	NM_001849.4	c.2769C>T	p.His923=	synonymous_variant	28/28	ENST00000300527.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A2	ENST00000300527.9	c.2769C>T	p.His923=	synonymous_variant	28/28	1	NM_001849.4	P1

Frequencies

GnomAD3 genomes AF: 0.00574 AC: 873 AN: 152210 Hom.: 6 Cov.: 34

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00996

Gnomad OTH AF: 0.00622

GnomAD3 exomes AF: 0.00507 AC: 1198 AN: 236200 Hom.: 4 AF XY: 0.00511 AC XY: 661 AN XY: 129304

Gnomad AFR exome AF: 0.00182

Gnomad AMR exome AF: 0.00204

Gnomad ASJ exome AF: 0.00472

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000401

Gnomad FIN exome AF: 0.00312

Gnomad NFE exome AF: 0.00900

Gnomad OTH exome AF: 0.00444

GnomAD4 exome AF: 0.00947 AC: 13774 AN: 1453880 Hom.: 77 Cov.: 34 AF XY: 0.00913 AC XY: 6602 AN XY: 723356

Gnomad4 AFR exome AF: 0.00165

Gnomad4 AMR exome AF: 0.00232

Gnomad4 ASJ exome AF: 0.00481

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000525

Gnomad4 FIN exome AF: 0.00366

Gnomad4 NFE exome AF: 0.0115

Gnomad4 OTH exome AF: 0.00723

GnomAD4 genome AF: 0.00573 AC: 873 AN: 152328 Hom.: 6 Cov.: 34 AF XY: 0.00537 AC XY: 400 AN XY: 74486

Gnomad4 AFR AF: 0.00212

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00415

Gnomad4 NFE AF: 0.00997

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00635 Hom.: 1

Bravo AF: 0.00539

Asia WGS AF: 0.00173 AC: 7 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

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)	Nov 16, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 26, 2021	This variant is associated with the following publications: (PMID: 15689448) -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	COL6A2: BP4, BP7, BS2 -

Myosclerosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Collagen 6-related myopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Bethlem myopathy 1A Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	1.1
Dann	Benign	0.84

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: rs140419176; hg19: chr21-47552175; COSMIC: COSV52430205; COSMIC: COSV52430205;