21-46112391-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001849.4(COL6A2):​c.528G>A​(p.Gln176Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,607,502 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 (★★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00026 ( 3 hom. )

Consequence

COL6A2
NM_001849.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.967
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 21-46112391-G-A is Benign according to our data. Variant chr21-46112391-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 258333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.967 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL6A2NM_001849.4 linkuse as main transcriptc.528G>A p.Gln176Gln synonymous_variant 3/28 ENST00000300527.9 NP_001840.3 P12110-1A0A384MDP3
COL6A2NM_058174.3 linkuse as main transcriptc.528G>A p.Gln176Gln synonymous_variant 3/28 NP_478054.2 P12110-2
COL6A2NM_058175.3 linkuse as main transcriptc.528G>A p.Gln176Gln synonymous_variant 3/28 NP_478055.2 P12110-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL6A2ENST00000300527.9 linkuse as main transcriptc.528G>A p.Gln176Gln synonymous_variant 3/281 NM_001849.4 ENSP00000300527.4 P12110-1

Frequencies

GnomAD3 genomes
AF:
0.000296
AC:
45
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00893
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000486
AC:
113
AN:
232480
Hom.:
1
AF XY:
0.000490
AC XY:
63
AN XY:
128676
show subpopulations
Gnomad AFR exome
AF:
0.0000724
Gnomad AMR exome
AF:
0.0000587
Gnomad ASJ exome
AF:
0.00871
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000203
Gnomad OTH exome
AF:
0.000695
GnomAD4 exome
AF:
0.000256
AC:
373
AN:
1455314
Hom.:
3
Cov.:
33
AF XY:
0.000256
AC XY:
185
AN XY:
723856
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000449
Gnomad4 ASJ exome
AF:
0.00834
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000846
Gnomad4 OTH exome
AF:
0.000948
GnomAD4 genome
AF:
0.000296
AC:
45
AN:
152188
Hom.:
0
Cov.:
32
AF XY:
0.000229
AC XY:
17
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00893
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00114
Hom.:
0
Bravo
AF:
0.000291
EpiCase
AF:
0.000327
EpiControl
AF:
0.000297

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Dec 08, 2016- -
Myosclerosis Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Collagen 6-related myopathy Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 22, 2024- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxNov 24, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
CADD
Benign
10
DANN
Benign
0.81

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: rs377585812; hg19: chr21-47532305; API