rs1042917
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBA1
The NM_001849.4(COL6A2):c.2039G>A(p.Arg680His) variant causes a missense change. The variant allele was found at a frequency of 0.483 in 1,612,622 control chromosomes in the GnomAD database, including 194,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R680?) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001849.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.2039G>A | p.Arg680His | missense_variant | 26/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.2039G>A | p.Arg680His | missense_variant | 26/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.2039G>A | p.Arg680His | missense_variant | 26/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.2039G>A | p.Arg680His | missense_variant | 26/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.2039G>A | p.Arg680His | missense_variant | 26/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.2039G>A | p.Arg680His | missense_variant | 25/27 | 5 | |||
COL6A2 | ENST00000413758.1 | c.710G>A | p.Arg237His | missense_variant | 11/11 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.445 AC: 67577AN: 151798Hom.: 16342 Cov.: 32
GnomAD3 exomes AF: 0.492 AC: 123178AN: 250564Hom.: 32074 AF XY: 0.482 AC XY: 65422AN XY: 135706
GnomAD4 exome AF: 0.487 AC: 711956AN: 1460706Hom.: 177685 Cov.: 72 AF XY: 0.483 AC XY: 350764AN XY: 726668
GnomAD4 genome ? AF: 0.445 AC: 67612AN: 151916Hom.: 16357 Cov.: 32 AF XY: 0.451 AC XY: 33455AN XY: 74220
ClinVar
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 31, 2012 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Bethlem myopathy 1A Benign:3
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Myosclerosis Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 30389748) - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 13, 2017 | - - |
Collagen 6-related myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Ullrich congenital muscular dystrophy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at