Variant chr21-46132203-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001849.4(COL6A2):c.2711C>T(p.Ala904Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 1,583,162 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

COL6A2
NM_001849.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 1.30

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A2	NM_001849.4 linkuse as main transcript	c.2711C>T	p.Ala904Val	missense_variant	28/28	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL6A2	ENST00000300527.9 linkuse as main transcript	c.2711C>T	p.Ala904Val	missense_variant	28/28	1	NM_001849.4	ENSP00000300527.4		P12110-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000336

AC:

AN:

196642

Hom.:

AF XY:

0.000242

AC XY:

AN XY:

107228

show subpopulations

Gnomad AFR exome

AF:

0.000175

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000142

Gnomad SAS exome

AF:

0.0000751

Gnomad FIN exome

AF:

0.000495

Gnomad NFE exome

AF:

0.000614

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000189

AC:

271

AN:

1430970

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

118

AN XY:

709750

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.0000496

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000532

Gnomad4 SAS exome

AF:

0.0000482

Gnomad4 FIN exome

AF:

0.000674

Gnomad4 NFE exome

AF:

0.000189

Gnomad4 OTH exome

AF:

0.000354

GnomAD4 genome

AF:

0.000125

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000350

AC:

ExAC

AF:

0.000640

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:3

Uncertain significance, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Aug 16, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 29, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Feb 14, 2020	- -

Bethlem myopathy 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.64

M_CAP

Pathogenic

0.29

MetaRNN

Uncertain

0.44

MetaSVM

Uncertain

0.33

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.63

Sift

Uncertain

0.026

Sift4G

Benign

0.086

Polyphen

1.0

Vest4

0.63

MVP

0.93

MPC

0.59

ClinPred

0.078

GERP RS

4.2

Varity_R

0.18

gMVP

0.69

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