rs35881321
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001849.4(COL6A2):c.679G>A(p.Asp227Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 1,611,910 control chromosomes in the GnomAD database, including 622 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.679G>A | p.Asp227Asn | missense_variant | 3/28 | ENST00000300527.9 | NP_001840.3 | |
COL6A2 | NM_058174.3 | c.679G>A | p.Asp227Asn | missense_variant | 3/28 | ENST00000397763.6 | NP_478054.2 | |
COL6A2 | NM_058175.3 | c.679G>A | p.Asp227Asn | missense_variant | 3/28 | NP_478055.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.679G>A | p.Asp227Asn | missense_variant | 3/28 | 1 | NM_001849.4 | ENSP00000300527 | P1 | |
COL6A2 | ENST00000397763.6 | c.679G>A | p.Asp227Asn | missense_variant | 3/28 | 5 | NM_058174.3 | ENSP00000380870 | ||
COL6A2 | ENST00000409416.6 | c.679G>A | p.Asp227Asn | missense_variant | 2/27 | 5 | ENSP00000387115 | |||
COL6A2 | ENST00000460886.1 | n.125G>A | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0262 AC: 3988AN: 151950Hom.: 69 Cov.: 32
GnomAD3 exomes AF: 0.0212 AC: 5195AN: 244682Hom.: 97 AF XY: 0.0212 AC XY: 2841AN XY: 133724
GnomAD4 exome AF: 0.0257 AC: 37489AN: 1459842Hom.: 553 Cov.: 34 AF XY: 0.0254 AC XY: 18454AN XY: 726296
GnomAD4 genome AF: 0.0263 AC: 3994AN: 152068Hom.: 69 Cov.: 32 AF XY: 0.0253 AC XY: 1881AN XY: 74342
ClinVar
Submissions by phenotype
not specified Benign:7
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 06, 2012 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2016 | 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. - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 06, 2017 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
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 12, 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 | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at