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21-46111185-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001849.4(COL6A2):c.-27-265G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 152,230 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 109 hom., cov: 33)

Consequence

COL6A2
NM_001849.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.17
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 -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 21-46111185-G-T is Benign according to our data. Variant chr21-46111185-G-T is described in ClinVar as [Benign]. Clinvar id is 1289874.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0263 (4001/152230) while in subpopulation NFE AF= 0.0299 (2035/68006). AF 95% confidence interval is 0.0288. There are 109 homozygotes in gnomad4. There are 2136 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd at 109 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COL6A2NM_001849.4 linkuse as main transcriptc.-27-265G>T intron_variant ENST00000300527.9
COL6A2NM_058174.3 linkuse as main transcriptc.-27-265G>T intron_variant ENST00000397763.6
LOC124905043XR_007067910.1 linkuse as main transcriptn.847C>A non_coding_transcript_exon_variant 1/2
COL6A2NM_058175.3 linkuse as main transcriptc.-27-265G>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COL6A2ENST00000300527.9 linkuse as main transcriptc.-27-265G>T intron_variant 1 NM_001849.4 P1P12110-1
COL6A2ENST00000397763.6 linkuse as main transcriptc.-27-265G>T intron_variant 5 NM_058174.3 P12110-2
COL6A2ENST00000436769.5 linkuse as main transcriptc.-27-265G>T intron_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0263
AC:
4003
AN:
152112
Hom.:
109
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00418
Gnomad AMI
AF:
0.00987
Gnomad AMR
AF:
0.0222
Gnomad ASJ
AF:
0.0740
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00623
Gnomad FIN
AF:
0.103
Gnomad MID
AF:
0.0665
Gnomad NFE
AF:
0.0299
Gnomad OTH
AF:
0.0215
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0263
AC:
4001
AN:
152230
Hom.:
109
Cov.:
33
AF XY:
0.0287
AC XY:
2136
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.00416
Gnomad4 AMR
AF:
0.0222
Gnomad4 ASJ
AF:
0.0740
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00644
Gnomad4 FIN
AF:
0.103
Gnomad4 NFE
AF:
0.0299
Gnomad4 OTH
AF:
0.0208
Alfa
AF:
0.0141
Hom.:
7
Bravo
AF:
0.0201
Asia WGS
AF:
0.00693
AC:
24
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJul 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
Cadd
Benign
0.31
Dann
Benign
0.73

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: rs112710668; hg19: chr21-47531099; API