rs140027285

Variant summary

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

The NM_001849.4(COL6A2):​c.1161C>T​(p.Ile387Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,611,530 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 34)
Exomes 𝑓: 0.0035 ( 15 hom. )

Consequence

COL6A2
NM_001849.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.35
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 -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 21-46118658-C-T is Benign according to our data. Variant chr21-46118658-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46118658-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.36 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 15 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL6A2NM_001849.4 linkc.1161C>T p.Ile387Ile synonymous_variant Exon 13 of 28 ENST00000300527.9 NP_001840.3 P12110-1A0A384MDP3
COL6A2NM_058174.3 linkc.1161C>T p.Ile387Ile synonymous_variant Exon 13 of 28 NP_478054.2 P12110-2
COL6A2NM_058175.3 linkc.1161C>T p.Ile387Ile synonymous_variant Exon 13 of 28 NP_478055.2 P12110-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL6A2ENST00000300527.9 linkc.1161C>T p.Ile387Ile synonymous_variant Exon 13 of 28 1 NM_001849.4 ENSP00000300527.4 P12110-1
COL6A2ENST00000397763.6 linkc.1161C>T p.Ile387Ile synonymous_variant Exon 13 of 28 5 ENSP00000380870.1 P12110-2
COL6A2ENST00000409416.6 linkc.1161C>T p.Ile387Ile synonymous_variant Exon 12 of 27 5 ENSP00000387115.1 P12110-3

Frequencies

GnomAD3 genomes
AF:
0.00224
AC:
341
AN:
152236
Hom.:
1
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000555
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000827
Gnomad FIN
AF:
0.00160
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00423
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00249
AC:
609
AN:
244506
Hom.:
6
AF XY:
0.00260
AC XY:
345
AN XY:
132886
show subpopulations
Gnomad AFR exome
AF:
0.000772
Gnomad AMR exome
AF:
0.000293
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00209
Gnomad FIN exome
AF:
0.00198
Gnomad NFE exome
AF:
0.00432
Gnomad OTH exome
AF:
0.00118
GnomAD4 exome
AF:
0.00355
AC:
5176
AN:
1459176
Hom.:
15
Cov.:
32
AF XY:
0.00344
AC XY:
2500
AN XY:
725726
show subpopulations
Gnomad4 AFR exome
AF:
0.000597
Gnomad4 AMR exome
AF:
0.000359
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00240
Gnomad4 FIN exome
AF:
0.00169
Gnomad4 NFE exome
AF:
0.00422
Gnomad4 OTH exome
AF:
0.00242
GnomAD4 genome
AF:
0.00224
AC:
341
AN:
152354
Hom.:
1
Cov.:
34
AF XY:
0.00208
AC XY:
155
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.000553
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000827
Gnomad4 FIN
AF:
0.00160
Gnomad4 NFE
AF:
0.00423
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00344
Hom.:
1
Bravo
AF:
0.00211
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jul 10, 2020
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30564623) -

Aug 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

COL6A2: BP4, BP7, BS2 -

not specified Benign:2
Oct 05, 2015
Eurofins Ntd Llc (ga)
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Myosclerosis Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Collagen 6-related myopathy Benign:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This 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
Jan 31, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
3.9
DANN
Benign
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs140027285; hg19: chr21-47538572; COSMIC: COSV56012526; COSMIC: COSV56012526; API