chr21-46003735-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_001848.3(COL6A1):c.2809A>G(p.Lys937Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00126 in 1,612,900 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K937R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001848.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A1 | NM_001848.3 | c.2809A>G | p.Lys937Glu | missense_variant | 35/35 | ENST00000361866.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A1 | ENST00000361866.8 | c.2809A>G | p.Lys937Glu | missense_variant | 35/35 | 1 | NM_001848.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000815 AC: 124AN: 152220Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000686 AC: 170AN: 247992Hom.: 1 AF XY: 0.000652 AC XY: 88AN XY: 134940
GnomAD4 exome AF: 0.00131 AC: 1909AN: 1460562Hom.: 2 Cov.: 34 AF XY: 0.00125 AC XY: 910AN XY: 726620
GnomAD4 genome ? AF: 0.000814 AC: 124AN: 152338Hom.: 0 Cov.: 34 AF XY: 0.000752 AC XY: 56AN XY: 74492
ClinVar
Submissions by phenotype
not provided Uncertain:5Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 25, 2021 | This variant is associated with the following publications: (PMID: 24036952, 30564623) - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 26, 2018 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Nov 08, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 19, 2018 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Bethlem myopathy 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at