Variant rs200902198 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001849.4(COL6A2):c.802-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,591,290 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 3 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.343

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:

COL6A2 (HGNC:):

COL6A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 21-46115827-C-T is Benign according to our data. Variant chr21-46115827-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
COL6A2	NM_001849.4 linkuse as main transcript	c.802-45C>T	intron_variant	ENST00000300527.9	NP_001840.3	P12110-1A0A384MDP3
COL6A2	NM_058174.3 linkuse as main transcript	c.802-45C>T	intron_variant		NP_478054.2	P12110-2
COL6A2	NM_058175.3 linkuse as main transcript	c.802-45C>T	intron_variant		NP_478055.2	P12110-3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
COL6A2	ENST00000300527.9 linkuse as main transcript	c.802-45C>T	intron_variant	1	NM_001849.4	ENSP00000300527.4	P12110-1
COL6A2	ENST00000397763.6 linkuse as main transcript	c.802-45C>T	intron_variant	5		ENSP00000380870.1	P12110-2
COL6A2	ENST00000409416.6 linkuse as main transcript	c.802-45C>T	intron_variant	5		ENSP00000387115.1	P12110-3
COL6A2	ENST00000485591.1 linkuse as main transcript	n.458-45C>T	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000227

AC:

AN:

237974

Hom.:

AF XY:

0.000239

AC XY:

AN XY:

129786

show subpopulations

Gnomad AFR exome

AF:

0.000198

Gnomad AMR exome

AF:

0.0000883

Gnomad ASJ exome

AF:

0.000309

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000233

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000322

Gnomad OTH exome

AF:

0.000688

GnomAD4 exome

AF:

0.000252

AC:

363

AN:

1439014

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

167

AN XY:

716942

show subpopulations

Gnomad4 AFR exome

AF:

0.000574

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.000231

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000217

Gnomad4 OTH exome

AF:

0.000353

GnomAD4 genome

AF:

0.000269

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000470

Hom.:

Bravo

AF:

0.000434

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.35

DANN

Benign

0.68

BranchPoint Hunter

3.0

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