rs748035948

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_001849.4(COL6A2):​c.1771-1G>A variant causes a splice acceptor, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

COL6A2
NM_001849.4 splice_acceptor, intron

Scores

5
1
1
Splicing: ADA: 1.000
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.22
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 21-46125265-G-A is Pathogenic according to our data. Variant chr21-46125265-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 17158.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr21-46125265-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL6A2NM_001849.4 linkc.1771-1G>A splice_acceptor_variant, intron_variant Intron 23 of 27 ENST00000300527.9 NP_001840.3 P12110-1A0A384MDP3
COL6A2NM_058174.3 linkc.1771-1G>A splice_acceptor_variant, intron_variant Intron 23 of 27 NP_478054.2 P12110-2
COL6A2NM_058175.3 linkc.1771-1G>A splice_acceptor_variant, intron_variant Intron 23 of 27 NP_478055.2 P12110-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL6A2ENST00000300527.9 linkc.1771-1G>A splice_acceptor_variant, intron_variant Intron 23 of 27 1 NM_001849.4 ENSP00000300527.4 P12110-1
COL6A2ENST00000397763.6 linkc.1771-1G>A splice_acceptor_variant, intron_variant Intron 23 of 27 5 ENSP00000380870.1 P12110-2
COL6A2ENST00000409416.6 linkc.1771-1G>A splice_acceptor_variant, intron_variant Intron 22 of 26 5 ENSP00000387115.1 P12110-3
COL6A2ENST00000413758.1 linkc.394-1G>A splice_acceptor_variant, intron_variant Intron 8 of 10 3 ENSP00000395751.1 H7C0M5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
37
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Ullrich congenital muscular dystrophy 1B Pathogenic:1
Jun 19, 2001
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.36
CADD
Pathogenic
32
DANN
Uncertain
0.99
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.93
FATHMM_MKL
Pathogenic
1.0
D
GERP RS
4.5

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.95
SpliceAI score (max)
0.88
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.88
Position offset: 1

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.

Other links and lift over

dbSNP: rs748035948; hg19: chr21-47545179; API