chr21-46120518-G-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_001849.4(COL6A2):āc.1336G>Cā(p.Asp446His) variant causes a missense change. The variant allele was found at a frequency of 0.000075 in 1,507,350 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D446N) has been classified as Likely benign.
Frequency
Consequence
NM_001849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.1336G>C | p.Asp446His | missense_variant | 16/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.1336G>C | p.Asp446His | missense_variant | 16/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.1336G>C | p.Asp446His | missense_variant | 16/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.1336G>C | p.Asp446His | missense_variant | 16/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.1336G>C | p.Asp446His | missense_variant | 16/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.1336G>C | p.Asp446His | missense_variant | 15/27 | 5 | |||
COL6A2 | ENST00000413758.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000361 AC: 55AN: 152176Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000837 AC: 9AN: 107528Hom.: 0 AF XY: 0.0000527 AC XY: 3AN XY: 56958
GnomAD4 exome AF: 0.0000428 AC: 58AN: 1355174Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 18AN XY: 667232
GnomAD4 genome AF: 0.000361 AC: 55AN: 152176Hom.: 0 Cov.: 34 AF XY: 0.000417 AC XY: 31AN XY: 74338
ClinVar
Submissions by phenotype
not provided Uncertain:6
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 17, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2021 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 02, 2018 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 23, 2022 | Reported as a variant of uncertain significance in an individual with limb-girdle muscular dystrophy 1A in the published literature; however, it is unclear if this individual harbored variants in other genes related to their phenotype (Nallamilli et al., 2018); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30564623) - |
Bethlem myopathy 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 14, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at