Variant rs757846451 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NM_001849.4(COL6A2):c.1348G>C(p.Glu450Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000143 in 1,491,650 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

COL6A2
NM_001849.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 3.92

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP6

Variant 21-46120530-G-C is Benign according to our data. Variant chr21-46120530-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 288611.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
COL6A2	NM_001849.4 linkuse as main transcript	c.1348G>C	p.Glu450Gln	missense_variant	16/28	ENST00000300527.9
COL6A2	NM_058174.3 linkuse as main transcript	c.1348G>C	p.Glu450Gln	missense_variant	16/28	ENST00000397763.6
COL6A2	NM_058175.3 linkuse as main transcript	c.1348G>C	p.Glu450Gln	missense_variant	16/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A2	ENST00000300527.9 linkuse as main transcript	c.1348G>C	p.Glu450Gln	missense_variant	16/28	1	NM_001849.4	P1	P12110-1
COL6A2	ENST00000397763.6 linkuse as main transcript	c.1348G>C	p.Glu450Gln	missense_variant	16/28	5	NM_058174.3		P12110-2
COL6A2	ENST00000409416.6 linkuse as main transcript	c.1348G>C	p.Glu450Gln	missense_variant	15/27	5			P12110-3
COL6A2	ENST00000413758.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000732

AC:

AN:

95582

Hom.:

AF XY:

0.0000599

AC XY:

AN XY:

50118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000165

Gnomad OTH exome

AF:

0.000396

GnomAD4 exome

AF:

0.000154

AC:

206

AN:

1339490

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

657874

show subpopulations

Gnomad4 AFR exome

AF:

0.0000698

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000190

Gnomad4 OTH exome

AF:

0.0000726

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000118

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000190

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 07, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Oct 14, 2020	- -

Bethlem myopathy 1A

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;.;.;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D;.;D

M_CAP

Pathogenic

0.31

MetaRNN

Uncertain

0.46

T;T;T;T

MetaSVM

Uncertain

0.16

MutationAssessor

Benign

-1.0

N;N;N;N

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.51

N;N;N;N

REVEL

Uncertain

0.47

Sift

Benign

0.46

T;T;T;T

Sift4G

Benign

0.46

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.36

MVP

0.99

MPC

0.61

ClinPred

0.27

GERP RS

4.4

Varity_R

0.19

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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