rs368064647
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_001849.4(COL6A2):c.638G>A(p.Arg213His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000354 in 1,611,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R213C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001849.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL6A2 | NM_001849.4 | c.638G>A | p.Arg213His | missense_variant | 3/28 | ENST00000300527.9 | |
COL6A2 | NM_058174.3 | c.638G>A | p.Arg213His | missense_variant | 3/28 | ENST00000397763.6 | |
COL6A2 | NM_058175.3 | c.638G>A | p.Arg213His | missense_variant | 3/28 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL6A2 | ENST00000300527.9 | c.638G>A | p.Arg213His | missense_variant | 3/28 | 1 | NM_001849.4 | P1 | |
COL6A2 | ENST00000397763.6 | c.638G>A | p.Arg213His | missense_variant | 3/28 | 5 | NM_058174.3 | ||
COL6A2 | ENST00000409416.6 | c.638G>A | p.Arg213His | missense_variant | 2/27 | 5 | |||
COL6A2 | ENST00000460886.1 | n.84G>A | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152068Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000492 AC: 12AN: 243762Hom.: 0 AF XY: 0.0000375 AC XY: 5AN XY: 133336
GnomAD4 exome AF: 0.0000343 AC: 50AN: 1459498Hom.: 0 Cov.: 33 AF XY: 0.0000427 AC XY: 31AN XY: 726134
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152068Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74262
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 17, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 30, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30564623) - |
Bethlem myopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 14, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL6A2 protein function. ClinVar contains an entry for this variant (Variation ID: 282526). This variant has not been reported in the literature in individuals affected with COL6A2-related conditions. This variant is present in population databases (rs368064647, gnomAD 0.008%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 213 of the COL6A2 protein (p.Arg213His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at