Variant chr21-46111301-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001849.4(COL6A2):c.-27-149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 587,398 control chromosomes in the GnomAD database, including 73,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16835 hom., cov: 33)

Exomes 𝑓: 0.50 ( 56774 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.290

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:

LOC124905043 (HGNC:):

LOC124905043 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=-0.81).

BP6

Variant 21-46111301-C-T is Benign according to our data. Variant chr21-46111301-C-T is described in ClinVar as [Benign]. Clinvar id is 679204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
COL6A2	NM_001849.4 linkuse as main transcript	c.-27-149C>T	intron_variant		ENST00000300527.9
COL6A2	NM_058174.3 linkuse as main transcript	c.-27-149C>T	intron_variant		ENST00000397763.6
LOC124905043	XR_007067910.1 linkuse as main transcript	n.731G>A	non_coding_transcript_exon_variant	1/2
COL6A2	NM_058175.3 linkuse as main transcript	c.-27-149C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
COL6A2	ENST00000300527.9 linkuse as main transcript	c.-27-149C>T	intron_variant	1	NM_001849.4	P1	P12110-1
COL6A2	ENST00000397763.6 linkuse as main transcript	c.-27-149C>T	intron_variant	5	NM_058174.3		P12110-2
COL6A2	ENST00000436769.5 linkuse as main transcript	c.-27-149C>T	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

67094

AN:

152054

Hom.:

16818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.581

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.542

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.644

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.457

GnomAD4 exome

AF:

0.501

AC:

217999

AN:

435226

Hom.:

56774

AF XY:

0.494

AC XY:

112774

AN XY:

228428

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.620

Gnomad4 ASJ exome

AF:

0.538

Gnomad4 EAS exome

AF:

0.413

Gnomad4 SAS exome

AF:

0.364

Gnomad4 FIN exome

AF:

0.637

Gnomad4 NFE exome

AF:

0.525

Gnomad4 OTH exome

AF:

0.497

GnomAD4 genome

AF:

0.441

AC:

67125

AN:

152172

Hom.:

16835

Cov.:

AF XY:

0.448

AC XY:

33306

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.190

Gnomad4 AMR

AF:

0.576

Gnomad4 ASJ

AF:

0.542

Gnomad4 EAS

AF:

0.428

Gnomad4 SAS

AF:

0.363

Gnomad4 FIN

AF:

0.644

Gnomad4 NFE

AF:

0.532

Gnomad4 OTH

AF:

0.453

Alfa

AF:

0.497

Hom.:

3034

Bravo

AF:

0.426

Asia WGS

AF:

0.400

AC:

1391

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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

-0.81

CADD

Benign

4.4

DANN

Benign

0.57

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