rs145460820

chr21-46132474-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001849.4(COL6A2):c.2982C>T(p.Ala994=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 1,606,538 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00032 (1 hom.)
• Consequence: COL6A2 NM_001849.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.06

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 21-46132474-C-T is Benign according to our data. Variant chr21-46132474-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 289156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46132474-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-4.06 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL6A2	NM_001849.4	c.2982C>T	p.Ala994=	synonymous_variant	28/28	ENST00000300527.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A2	ENST00000300527.9	c.2982C>T	p.Ala994=	synonymous_variant	28/28	1	NM_001849.4	P1

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152244 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000483 AC: 116 AN: 240238 Hom.: 1 AF XY: 0.000488 AC XY: 64 AN XY: 131176

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000349

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000549

Gnomad SAS exome AF: 0.000855

Gnomad FIN exome AF: 0.000489

Gnomad NFE exome AF: 0.000606

Gnomad OTH exome AF: 0.000503

GnomAD4 exome AF: 0.000320 AC: 465 AN: 1454176 Hom.: 1 Cov.: 34 AF XY: 0.000337 AC XY: 244 AN XY: 723098

Gnomad4 AFR exome AF: 0.0000599

Gnomad4 AMR exome AF: 0.000314

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000906

Gnomad4 FIN exome AF: 0.000307

Gnomad4 NFE exome AF: 0.000304

Gnomad4 OTH exome AF: 0.000299

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152362 Hom.: 0 Cov.: 34 AF XY: 0.000483 AC XY: 36 AN XY: 74502

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000827

Gnomad4 FIN AF: 0.00103

Gnomad4 NFE AF: 0.000823

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000492 Hom.: 0

Bravo AF: 0.000283

EpiCase AF: 0.000327

EpiControl AF: 0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	COL6A2: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 24, 2019	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 18, 2016

- -

Bethlem myopathy 1A Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	1.3
Dann	Benign	0.92

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: rs145460820; hg19: chr21-47552388; COSMIC: COSV52423417; COSMIC: COSV52423417;