rs115957676
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001849.4(COL6A2):c.499G>A(p.Gly167Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000558 in 1,608,264 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G167C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.499G>A | p.Gly167Ser | missense_variant | 3/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.499G>A | p.Gly167Ser | missense_variant | 3/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.499G>A | p.Gly167Ser | missense_variant | 3/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.499G>A | p.Gly167Ser | missense_variant | 3/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.499G>A | p.Gly167Ser | missense_variant | 3/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.499G>A | p.Gly167Ser | missense_variant | 2/27 | 5 | |||
COL6A2 | ENST00000436769.5 | c.499G>A | p.Gly167Ser | missense_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00276 AC: 419AN: 152056Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000714 AC: 168AN: 235134Hom.: 3 AF XY: 0.000532 AC XY: 69AN XY: 129766
GnomAD4 exome AF: 0.000329 AC: 479AN: 1456090Hom.: 5 Cov.: 33 AF XY: 0.000308 AC XY: 223AN XY: 724080
GnomAD4 genome ? AF: 0.00275 AC: 419AN: 152174Hom.: 1 Cov.: 32 AF XY: 0.00247 AC XY: 184AN XY: 74404
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 02, 2017 | This 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 submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 11, 2015 | - - |
Myosclerosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
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. - |
Bethlem myopathy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
COL6A2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 10, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at