chr21-46125432-C-T

Variant summary

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

The NM_001849.4(COL6A2):​c.1817-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.052 in 1,611,024 control chromosomes in the GnomAD database, including 5,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 616 hom., cov: 33)
Exomes 𝑓: 0.050 ( 5043 hom. )

Consequence

COL6A2
NM_001849.4 intron

Scores

15

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.74
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004430741).
BP6
Variant 21-46125432-C-T is Benign according to our data. Variant chr21-46125432-C-T is described in ClinVar as [Benign]. Clinvar id is 93924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46125432-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COL6A2NM_001849.4 linkuse as main transcriptc.1817-33C>T intron_variant ENST00000300527.9
COL6A2NM_058174.3 linkuse as main transcriptc.1817-33C>T intron_variant ENST00000397763.6
COL6A2NM_058175.3 linkuse as main transcriptc.1817-33C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COL6A2ENST00000300527.9 linkuse as main transcriptc.1817-33C>T intron_variant 1 NM_001849.4 P1P12110-1
COL6A2ENST00000397763.6 linkuse as main transcriptc.1817-33C>T intron_variant 5 NM_058174.3 P12110-2
COL6A2ENST00000413758.1 linkuse as main transcriptc.455C>T p.Pro152Leu missense_variant 10/113
COL6A2ENST00000409416.6 linkuse as main transcriptc.1817-33C>T intron_variant 5 P12110-3

Frequencies

GnomAD3 genomes
AF:
0.0663
AC:
10059
AN:
151834
Hom.:
614
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0858
Gnomad AMI
AF:
0.0713
Gnomad AMR
AF:
0.0760
Gnomad ASJ
AF:
0.0401
Gnomad EAS
AF:
0.348
Gnomad SAS
AF:
0.0925
Gnomad FIN
AF:
0.0252
Gnomad MID
AF:
0.0696
Gnomad NFE
AF:
0.0361
Gnomad OTH
AF:
0.0824
GnomAD3 exomes
AF:
0.0753
AC:
18789
AN:
249494
Hom.:
1583
AF XY:
0.0724
AC XY:
9797
AN XY:
135312
show subpopulations
Gnomad AFR exome
AF:
0.0908
Gnomad AMR exome
AF:
0.0896
Gnomad ASJ exome
AF:
0.0347
Gnomad EAS exome
AF:
0.339
Gnomad SAS exome
AF:
0.0820
Gnomad FIN exome
AF:
0.0257
Gnomad NFE exome
AF:
0.0379
Gnomad OTH exome
AF:
0.0577
GnomAD4 exome
AF:
0.0505
AC:
73631
AN:
1459070
Hom.:
5043
Cov.:
37
AF XY:
0.0512
AC XY:
37190
AN XY:
725804
show subpopulations
Gnomad4 AFR exome
AF:
0.0864
Gnomad4 AMR exome
AF:
0.0894
Gnomad4 ASJ exome
AF:
0.0368
Gnomad4 EAS exome
AF:
0.408
Gnomad4 SAS exome
AF:
0.0788
Gnomad4 FIN exome
AF:
0.0253
Gnomad4 NFE exome
AF:
0.0338
Gnomad4 OTH exome
AF:
0.0591
GnomAD4 genome
AF:
0.0662
AC:
10063
AN:
151954
Hom.:
616
Cov.:
33
AF XY:
0.0682
AC XY:
5066
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.0856
Gnomad4 AMR
AF:
0.0759
Gnomad4 ASJ
AF:
0.0401
Gnomad4 EAS
AF:
0.348
Gnomad4 SAS
AF:
0.0924
Gnomad4 FIN
AF:
0.0252
Gnomad4 NFE
AF:
0.0361
Gnomad4 OTH
AF:
0.0839
Alfa
AF:
0.0448
Hom.:
77
Bravo
AF:
0.0731
TwinsUK
AF:
0.0326
AC:
121
ALSPAC
AF:
0.0374
AC:
144
ESP6500AA
AF:
0.0867
AC:
382
ESP6500EA
AF:
0.0388
AC:
334
ExAC
AF:
0.0751
AC:
9111
Asia WGS
AF:
0.169
AC:
587
AN:
3478
EpiCase
AF:
0.0412
EpiControl
AF:
0.0389

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Nov 16, 2012- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxJun 16, 2018This 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. -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
0.057
DANN
Benign
0.68
DEOGEN2
Benign
0.030
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0054
N
LIST_S2
Benign
0.29
T
MetaRNN
Benign
0.0044
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
P;P;P;P;P
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.096
Sift
Benign
0.13
T
Sift4G
Benign
0.13
T
ClinPred
0.0069
T
GERP RS
-3.5

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.

Other links and lift over

dbSNP: rs2276101; hg19: chr21-47545346; COSMIC: COSV56014201; API