21-46112622-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001849.4(COL6A2):c.714+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 1,601,862 control chromosomes in the GnomAD database, including 6,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 1193 hom., cov: 32)

Exomes 𝑓: 0.052 ( 4965 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.278

Variant links:

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]

COL6A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 21-46112622-C-T is Benign according to our data. Variant chr21-46112622-C-T is described in ClinVar as [Benign]. Clinvar id is 93958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46112622-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COL6A2	NM_001849.4 link	c.714+45C>T	intron_variant	Intron 3 of 27	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3
COL6A2	NM_058174.3 link	c.714+45C>T	intron_variant	Intron 3 of 27		NP_478054.2	P12110-2
COL6A2	NM_058175.3 link	c.714+45C>T	intron_variant	Intron 3 of 27		NP_478055.2	P12110-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9 link	c.714+45C>T		intron_variant	Intron 3 of 27	1	NM_001849.4	ENSP00000300527.4		P12110-1

Frequencies

GnomAD3 genomes

AF:

0.0967

AC:

14698

AN:

152034

Hom.:

1191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.0716

Gnomad AMR

AF:

0.0963

Gnomad ASJ

AF:

0.0369

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.0876

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0358

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.0804

AC:

19368

AN:

240852

Hom.:

1502

AF XY:

0.0754

AC XY:

9939

AN XY:

131752

show subpopulations

Gnomad AFR exome

AF:

0.204

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.0327

Gnomad EAS exome

AF:

0.289

Gnomad SAS exome

AF:

0.0817

Gnomad FIN exome

AF:

0.0187

Gnomad NFE exome

AF:

0.0379

Gnomad OTH exome

AF:

0.0599

GnomAD4 exome

AF:

0.0524

AC:

76026

AN:

1449708

Hom.:

4965

Cov.:

AF XY:

0.0527

AC XY:

38028

AN XY:

721420

show subpopulations

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.0337

Gnomad4 EAS exome

AF:

0.366

Gnomad4 SAS exome

AF:

0.0783

Gnomad4 FIN exome

AF:

0.0191

Gnomad4 NFE exome

AF:

0.0338

Gnomad4 OTH exome

AF:

0.0654

GnomAD4 genome

AF:

0.0967

AC:

14720

AN:

152154

Hom.:

1193

Cov.:

AF XY:

0.0972

AC XY:

7234

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.0960

Gnomad4 ASJ

AF:

0.0369

Gnomad4 EAS

AF:

0.294

Gnomad4 SAS

AF:

0.0879

Gnomad4 FIN

AF:

0.0183

Gnomad4 NFE

AF:

0.0358

Gnomad4 OTH

AF:

0.109

Alfa

AF:

0.0238

Hom.:

Bravo

AF:

0.109

Asia WGS

AF:

0.163

AC:

567

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Nov 16, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.8

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over